Tracheal cancer: clinical guidelines

List of Abbreviations

IV – intravenous

WHO – World Health Organization

EBRT – external beam radiotherapy

CT – computed tomography

PT – physical therapy

MRI – magnetic resonance imaging

SFD – single focal dose

TFD – total focal dose

LCE – level of confidence of evidence

US – ultrasound examination

GRS – grade of recommendation strength

EBLT – endobronchial laser therapy

AUC – Area Under Curve

BED – Biologically Effective Dose

ECOG – Eastern Cooperative Oncology Group

RUSSCO – Russian Society of Clinical Oncology

TNM – (abbreviation for tumor, nodus, and metastasis) international staging system for cancer

** – vital and essential drugs

# – drug used not in accordance with the indications

and contraindications, routes of administration, and dosages contained

in the drug instructions for use (off-label)

Terms and Definitions

Adjuvant chemotherapy – a type of chemotherapy administered after complete surgical removal of the primary tumor to eliminate micrometastases.

Stage II rehabilitation – rehabilitation in inpatient settings of medical organizations (rehabilitation centers, rehabilitation departments) during the early recovery period of the disease, the late rehabilitation period, or the period of residual effects of the disease.

Neoadjuvant chemotherapy – administered immediately before surgical removal of the primary tumor to devitalize the tumor and control micrometastasis.

R1 resection – removal of the affected organ within healthy tissues along with regional lymph node basins with microscopically positive resection margins (residual tumor present).

R2 resection – removal of the affected organ along with regional lymph node basins leaving macroscopically visible tumor manifestations.

First stage of rehabilitation – rehabilitation during the period of specialized treatment for the primary disease (including surgical treatment / chemotherapy / radiation therapy) in departments of medical organizations specialized in the primary disease.

Prehabilitation – rehabilitation from the moment of diagnosis until the start of treatment (surgery/chemotherapy/radiation therapy).

Radical surgery (R0) – removal of the affected organ within healthy tissues along with regional lymph node basins without micro- or macroscopic manifestations of the tumor process.

Sternotomy – a surgical approach to the thoracic organs involving the transection of the sternum.

Stage III rehabilitation – rehabilitation during the early and late rehabilitation periods, and the period of residual effects of the disease in departments (rooms) of rehabilitation, physiotherapy, exercise therapy, reflexology, manual therapy, psychotherapy, medical psychology, speech therapy/phonopedics (speech-language pathology, phoniatrics) providing outpatient medical care, day care hospitals, and by mobile teams at home (including sanatorium-resort settings).

1. Brief information on the disease or condition

1.1 Definition of the disease or condition

Tracheal cancer – a nosological group of malignant epithelial tumors of the trachea [1].

1.2 Etiology and pathogenesis of the disease or condition (group of diseases or conditions)

As with other oncological diseases, the causes of malignant tumors affecting the respiratory system remain unknown to date. However, statistical studies of a large group of patients with this pathology have identified risk factors predisposing to the development of the disease [2,3]. Risk groups include individuals:

1. aged 40–60 years;

2. using tobacco products in any form – cigars and cigarettes, pipe tobacco, chewing tobacco, and snuff;

3. exposed to radiotherapy and radiation;

4. with constant occupational exposure to wood, nickel, or asbestos dust;

5. infected with oncogenic types of viruses.

1.3 Epidemiology of the Disease or Condition

The incidence of tracheal cancer accounts for less than 1% among patients with respiratory tract malignancies. Exact incidence data for tracheal cancer are lacking because cases are registered together with lung cancer patients [1,4].

1.4 Features of Coding the Disease or Condition

C33 Malignant neoplasm of trachea

1.5 Classification of the disease or condition

According to the WHO histological classification (2015), the following are distinguished:

1. Squamous cell carcinoma.

2. Adenoid cystic carcinoma.

3. Mucoepidermoid carcinoma.

According to the clinical and anatomical classification, lesions are distinguished in:

1. Cervical trachea.

2. Upper thoracic trachea.

3. Mid-thoracic trachea.

4. Lower thoracic trachea.

Tumor grade:

• Gx – grade cannot be assessed;

• G1 – well-differentiated tumor;

• G2 – moderately differentiated tumor;

• G3 – poorly differentiated tumor;

• G4 – undifferentiated tumor.

There is no TNM staging classification (Union for International Cancer Control) for tracheal cancer.

1.6 Clinical presentation of the disease or condition

Clinical manifestations of malignant tracheal tumors depend mainly on the direction of growth, mobility, presence or absence of ulceration and breakdown, and most importantly, on the size and degree of stenosis of the organ lumen.

The most characteristic symptom is difficulty breathing – dyspnea and even stridor. Typically, these occur only when the lumen is narrowed by 2/3 or more. Slow growth with gradual compensation of respiratory function in some cases allows patients to continue working with pronounced tracheostenosis. Good adaptability to the gradual narrowing of the tracheal lumen is one of the main reasons for the delayed diagnosis of tracheal tumors.

Dyspnea in malignant tracheal tumors, unlike that in bronchial asthma and pulmonary emphysema, is more often inspiratory. It usually develops gradually, but always noticeably worsens with physical exertion: fast walking, climbing stairs, and sometimes even talking. An increase in dyspnea is regularly noted during influenza, bronchitis, and sputum accumulation. In the supine position, many patients experience attacks of asphyxia that occur without blood eosinophilia, respond poorly to bronchodilators, and usually stop after the expectoration of sputum containing no eosinophils or Curschmann spirals. Due to such attacks, patients with tracheal tumors are often treated for a long time for misdiagnosed asthmatic bronchitis and especially frequently bronchial asthma. Therefore, individuals with dyspnea that cannot be clearly attributed to heart or lung disease must be examined to confirm or rule out a tracheal tumor.

With sharp narrowing of the tracheal lumen, a typical picture of stridor develops, sometimes with pulmonary emphysema or atelectasis. Secondary bronchitis and pneumonia are frequent. There are cases where recurrent pneumonia poorly responding to antibiotic therapy (J01: Antibacterials for systemic use) was the first clinical manifestation of a tracheal tumor.

Relatively early, patients with tracheal tumors begin to complain of a cough that worsens with changes in body position and displacement during palpation. The cough can be persistent, often agonizing, dry, or productive. In cases of tumor breakdown, the sputum acquires a putrid odor. Sometimes patients cough up pieces of tumor, after which breathing relief occurs. In almost half of the patients, hemoptysis is observed in the form of streaks or admixture of blood in the sputum.

Pain is generally absent in tracheal tumors. Only a sensation of chest tightness or pressure in the neck region is noted.

In a number of cases, a change in voice timbre is noted, the cause of which may be compression or invasion of the recurrent laryngeal nerve by the tumor.

When the tumor is located on the posterior wall, swallowing difficulties and pain may occur.

All the above symptoms of tracheal tumors have been combined since 1959 into the so-called tracheal syndrome. The average time interval from the first symptoms of malignant tracheal tumors to the appearance of pronounced "tracheal syndrome" does not exceed 8 months.

In patients with malignant tracheal tumors in advanced stages, decreased appetite, weakness, weight loss, fever, and symptoms of damage to neighboring organs, particularly the esophagus, are observed. However, in most cases, death from asphyxia or pneumonia occurs earlier.

2. Diagnostics, medical indications and contraindications for diagnostic methods

Due to its low incidence, there are no screening programs for the detection of tracheal cancer.

Criteria for establishing the diagnosis/condition: there are no pathognomonic symptoms.

2.1 Complaints and Anamnesis

Comments: tracheal cancer is characterized by a gradual onset and a prolonged asymptomatic course. The most common complaint is difficulty breathing, but due to the gradual narrowing of the tracheal lumen, the clinical manifestations of this symptom may appear when obstruction exceeds 1/2 of the tracheal diameter.

2.2 Physical Examination

2.3 Laboratory Diagnostics

2.4 Instrumental Diagnostics

Comments: to obtain an adequate amount of material, several (3–5) biopsies should be performed using standard endoscopic forceps.

Comments: If metastatically affected lymph nodes are detected and technically feasible, fine-needle aspiration biopsy is recommended. The treatment plan should not be formulated until biopsy results are obtained. In case of submucosal infiltrative tumor growth, a false-negative result is possible, which requires a repeat deep biopsy. The sensitivity and specificity of the method increase when modern endoscopic imaging technologies are used (magnifying endoscopy, hyperspectral bronchoscopy, chromoendoscopy, autofluorescence bronchoscopy).

Comments: Ultrasound of the cervical-supraclavicular regions and abdominal organs is the diagnostic standard for tracheal cancer when CT/MRI diagnostics cannot be performed

2.5 Other Procedures

1. Distance to the proximal and distal resection margins.

2. Tumor dimensions.

3. Histological structure of the tumor.

4. Tumor grade (degree of differentiation).

5. Presence of proximal resection margin involvement (a negative result must also be stated).

6. Presence of distal resection margin involvement (a negative result must also be stated).

7. Presence of lymphovascular or perineural invasion (a negative result must also be explicitly stated).

8. Degree of tumor regression according to the Mandard/Dworak scales (Appendix G6) (if prior combined treatment was administered).

9. Involvement of the apical lymph node (a negative result must also be stated) [13,14].

GPR CLOE 5Grade of Recommendations – C (Level of Evidence – 5)

The indicators of tumor regression grades are presented below:

Table 1. Evaluation of tumor regression grade in pathohistological examination using the Mandard and Dworak scales

3. Treatment, including drug and non-drug therapies, diet therapy, and pain management

In the absence of medical contraindications, surgical intervention is accompanied by the prophylaxis of infectious complications using antibacterial drugs (J01: Antibacterials for systemic use).

Depending on clinical indications, adjuvant/neoadjuvant chemotherapy, radiotherapy, or a combination thereof is additionally performed (see relevant sections).

Radical surgical treatment generally does not require additional antineoplastic therapy, although according to several authors, the administration of postoperative radiotherapy in all cases improves long-term outcomes compared to isolated radical surgery.

When performing palliative surgery (malignant tumor cells left at the resection margin), it is advisable to supplement the surgery with radiotherapy, which improves long-term outcomes compared to isolated palliative surgery.

Five-year survival after radical surgery is 65–85% for adenoid cystic carcinoma and does not exceed 40% for squamous cell carcinoma [15–17].

3.1 Surgical Treatment

When the tumor is localized in the thoracic and cervical regions, surgery is performed via a transsternal approach: full median sternotomy or partial median sternotomy, with circular resection of the trachea considered an adequate extent of surgery. For tumors located in the middle and lower thirds of the trachea, a lateral or posterolateral thoracotomy through the 4th intercostal space may be used. When the tumor is located at the tracheal bifurcation, circular resection of the tracheal bifurcation with Y-shaped reconstruction of the tracheal carina may be performed.

• If the tumor extends to the right main bronchus and the latter cannot be mobilized to construct a safe anastomosis, it is recommended to perform a circular resection of the tracheal bifurcation with right pneumonectomy via a lateral thoracotomy through the 4th or 5th intercostal space [9].

GCP CLoE 5Grading of Recommendations Assessment, Development and Evaluation (GRADE) – C (Level of Evidence – 5)

• In early tracheal cancer, it is recommended to consider organ-preserving and function-sparing treatment modalities (such as endoscopic photodynamic therapy of the tracheal and/or upper respiratory tract tumor; endoscopic combined surgery: electrosection, argon plasma coagulation, and photodynamic therapy of the tracheal tumor; endoscopic laser surgery for tracheal diseases) with high efficacy [18].

GPR CLOE 5Grade of Recommendations – C (Level of Evidence – 5)

Comments: prognostic factors must be taken into account when determining the treatment strategy [19]. Negative prognostic factors include the following:

- degree of differentiation >G3;

- presence of tumor at the resection margin;

- lymphatic, vascular, or perineural invasion [16].

• In resectable localized and locally advanced tracheal cancer, in the absence of absolute contraindications, surgical treatment is recommended as the first stage; the scope of surgery is determined by the tumor localization and local extension [5, 17].

GCP CLoE 5Grading of Recommendations Assessment, Development and Evaluation (GRADE) – C (Level of Evidence – 5)

• In unresectable tracheal cancer, chemoradiotherapy is recommended, including the primary lesion in the irradiation volume with a 2.0 cm margin from the tumor edges and metastatic regional lymph nodes. After a 2-week break, the treatment response is assessed (see Appendix G3) and a decision on surgical treatment is made. If surgery is unfeasible, continuation of standalone radical radiotherapy with or without chemotherapy should be pursued. Radical radiotherapy involves combined radiotherapeutic intervention: endobronchial radiotherapy (EBRT) + external beam radiotherapy (EBRT) delivering a biologically equivalent dose BED₁₀ = 50–90 Gy [20–25].

GRC CLEL 4Grade of Recommendation – C (Level of Evidence – 4)

Comments: treatment strategy must take into account the presence of complications associated with tumor extent.

• In functionally inoperable tracheal cancer (in the presence of severe comorbid pathology), conservative treatment or supportive care is recommended (based on the patient's performance status assessment – see Appendix G1, G2). In the presence of absolute contraindications to radiotherapy, tracheal stenting in the tumor-affected area or tracheostomy creation may be performed [5, 8].

GCP CLoE 5Grading of Recommendations Assessment, Development and Evaluation (GRADE) – C (Level of Evidence – 5)

Comments: the risk of surgery outweighs the risk associated with cancer progression. The decision regarding contraindications to surgical treatment can be made only by a multidisciplinary team (tumor board) comprising a surgeon, physician, anesthesiologist, and intensivist.

3.2 Pharmacotherapy

Chemotherapy has low efficacy in patients with diagnosed tracheal cancer and is therefore practically not used. Only a few reports have been published demonstrating the efficacy of combination chemotherapy with the regimen #paclitaxel** 45-50 mg/m² + #карбоплатин** area under the concentration–time curve (Area Under Curve) (AUC) 1.5-2.

• This type of treatment is extremely rarely used as a monotherapy. It is recommended in combination with radiotherapy for the treatment of unresectable tracheal cancer [26–28].

GRC CLEL 4Grade of Recommendation – C (Level of Evidence – 4)

3.3 Radiotherapy

It should be noted that malignant neoplasms of the trachea are relatively radiosensitive tumors (especially adenoid cystic carcinoma), for which radiotherapy can and, in certain clinical situations, must be used both as an adjuvant therapeutic modality and as a standalone radical treatment. Radical radiotherapy involves combined radiotherapeutic intervention: EBRT + external beam radiotherapy delivering a biologically equivalent dose BED₁₀ = 50–90 Gy. Modern conformal radiotherapy techniques allow for selective irradiation of the tumor with maximal protection of adjacent tissues. Dosimetric verification of the calculated radiotherapy plan is performed.

• Following non-radical or marginally radical surgeries, external beam radiotherapy is recommended (fraction dose = 2 Gy, total dose = 44 Gy) with inclusion of the primary lesion based on pre-treatment CT data in the irradiation volume, with a 2.0 cm margin from the tumor edge. If residual tumor is present locally or with the assistance of brachytherapy, up to a total dose of 50–55 Gy [24, 27].

Following surgical treatment when:

• R0 – radiotherapy is not indicated;

• R1 – endobronchial radiotherapy of the resection margin;

• R2 – combined radical radiotherapy delivering BED₁₀ = 50–90 Gy.

GRC CLEL 4Grade of Recommendation – C (Level of Evidence – 4)

• In unresectable locally advanced tumors with metastatic regional lymph nodes or comorbid pathology (functional contraindications to surgery), radiotherapy (3D conformal) is recommended with the inclusion of the primary lesion, with a 2.0 cm margin from the tumor edges and metastatic lymph nodes, in the irradiation volume [24,29].

Level of Recommendations – CLevel of Evidence – 4Level of Recommendations – C (Level of Evidence – 4)

• In recurrent tumors or upon achieving marked remission after the initial irradiation phase to a total dose of 44 Gy, localized treatment using external beam or brachytherapy radiation units is recommended [24,29].

GRC CLEL 4Grade of Recommendation – C (Level of Evidence – 4)

3.4 Other treatment

3.4.1 Symptomatic therapy

• Patients with acute bleeding are recommended to undergo urgent endoscopic examination (tracheobronchoscopy) and systemic hemostatic therapy. Depending on the examination results, endoscopic hemostasis is performed using thermo-/electrocoagulation or laser photocoagulation. If endoscopic hemostasis is impossible or ineffective, emergency surgery is performed [30].

GCP CLoE 5Grading of Recommendations Assessment, Development and Evaluation (GRADE) – C (Level of Evidence – 5)

• In case of tumor stenosis and the inability to perform surgical treatment, it is recommended to place a self-expanding stent in the area of tumor stenosis or perform symptomatic surgical treatment (placement of a temporary/permanent tracheostomy) [31].

Level of Recommendations – CLevel of Evidence – 4Level of Recommendations – C (Level of Evidence – 4)

• In case of tumor stenosis, endoscopic recanalization is recommended (recanalization of the trachea and/or endoscopic laser destruction of the tracheal tumor and/or removal of the tracheal neoplasm by laser destruction), which can be performed both in inoperable tumors and as part of preoperative preparation to normalize respiration and improve the patient's functional parameters [30,32,33].

GIB CLOE 4Grade of Recommendation – C (Level of Evidence – 4)

Comments: the goal of so-called "supportive" care is to prevent and relieve symptoms of the disease, and to maintain the quality of life of patients and their families, regardless of the stage of the disease and the need for other types of therapy. In the case of tracheal cancer, measures aimed at alleviating core symptoms help increase life expectancy.

3.4.2 Pain management

Principles of analgesia and optimal choice of analgesic therapy in patients with tracheal cancer presenting with chronic pain syndrome (see Appendix G4, G5) correspond to the principles of analgesia set forth in the guidelines "Practical Recommendations for the Treatment of Chronic Pain Syndrome in Cancer Patients" (Authors: Kogonia L.M., Voloshin A.G., Novikov G.A., Sidorov A.V., DOI: 10.18027/2224-5057-2018-8-3s2-617-635, https://rosoncoweb.ru/standarts/ Russian Society of Clinical Oncology RUSSCO/2018/2018-47.pdf).

3.4.3 Diet therapy

To date, no reliable data have been obtained regarding the effect of dietary habits on the risk of developing tracheal cancer or the risk of recurrence or progression of this disease in individuals with an established diagnosis. In this regard, any changes in the patients' usual diet are not recommended, unless they are dictated by the need to correct comorbid conditions or to manage/prevent complications of ongoing treatment (surgical, medical, or radiation).

3.4.4 Supportive care

Principles of treatment and prevention of nausea and vomiting in patients with tracheal cancer correspond to the principles set forth in the guidelines "Prevention and Treatment of Nausea and Vomiting" (Authors: Vladimirova L.Yu., Gladkov O.A., Kogonia L.M., Koroleva I.A., Semiglazova T.Yu. DOI: 10.18027/2224-5057-2018-8-3s2-502-511, https://rosoncoweb.ru/standarts/RUSSCO/2018/2018-35.pdf).

Principles of treatment and prevention of bone complications in patients with tracheal cancer correspond to the principles set forth in the guidelines "Use of Osteomodifying Agents for the Prevention and Treatment of Bone Pathology in Malignant Neoplasms" (Authors: Manzyuk L.V., Bagrova S.G., Kopp M.V., Kutukova S.I., Semiglazova T.Yu. DOI: 10.18027/2224-5057-2018-8-3s2-512-520, https://rosoncoweb.ru/standarts/RUSSCO/2018/2018-36.pdf).

Principles of prevention and treatment of infectious complications and febrile neutropenia in patients with tracheal cancer correspond to the principles set forth in the guidelines "Treatment of Infectious Complications of Febrile Neutropenia and Administration of Colony-Stimulating Factors" (Authors: Sakaeva D.D., Orlova R.V., Shabaeva M.M. DOI: 10.18027 / 2224-5057-2018-8-3s2-521-530, https://rosoncoweb.ru/standarts/RUSSCO/2018/2018-37.pdf).

Principles of prevention and treatment of hepatotoxicity in patients with tracheal cancer correspond to the principles set forth in the guidelines "Management of Hepatotoxicity" (Authors: Tkachenko P.E., Ivashkin V.T., Maevskaya M.V. DOI: 10.18027/2224-5057-2018-8-3s2-531-544, https://rosoncoweb.ru/standarts/RUSSCO/2018/2018-38.pdf).

Principles of prevention and treatment of cardiovascular complications in patients with tracheal cancer correspond to the principles set forth in the guidelines "Practical Recommendations for the Management of Cardiovascular Toxicity of Antineoplastic Drug Therapy" (Authors: Vitsenya M.V., Ageev F.T., Gilyarov M.Yu., Ovchinnikov A.G., Orlova R.V., Poltavskaya M.G., Sycheva E.A. DOI: 10.18027/2224-5057-2018-8-3s2-545-563, https://rosoncoweb.ru/standarts/RUSSCO/2018/2018-39.pdf).

Principles of prevention and treatment of skin complications in patients with tracheal cancer correspond to the principles set forth in the guidelines "Practical Recommendations for the Drug Treatment of Dermatological Reactions in Patients Receiving Antineoplastic Drug Therapy" (Authors: Koroleva I.A., Bolotina L.V., Gladkov O.A., Gorbunova V.A., Kruglova L.S., Manzyuk L.V., Orlova R.V. DOI: 10.18027/2224-5057-2018-8-3s2-564-574, https://rosoncoweb.ru/standarts/RUSSCO/2018/2018-40.pdf).

The principles of nutritional support in patients with tracheal cancer correspond to the principles outlined in the guidelines "Practical Guidelines for Nutritional Support in Cancer Patients" (Authors: Sytov A.V., Leiderman I.N., Lomidze S.V., Nekhaev I.V., Khoteev A.Zh. DOI: 10.18 027/2224–5057–2018–8–3s2–575–583, https://rosoncoweb.ru/standarts/RUSSCO/2018/2018-41.pdf).

The principles of prevention and treatment of nephrotoxicity in patients with tracheal cancer correspond to the principles outlined in the guidelines "Practical Guidelines for the Management of Antineoplastic Drug-Induced Nephrotoxicity" (Authors: Gromova E.G., Biryukova L.S., Dzhumabaeva B.T., Kurmukov I.A. DOI: 10.18 027 / 2224–5057–2018–8–3s2–591–603, https://rosoncoweb.ru/ standarts/RUSSCO/2018/2018-44.pdf).

The principles of prevention and treatment of thromboembolic events in patients with tracheal cancer correspond to the principles outlined in the guidelines "Practical Guidelines for the Prevention and Treatment of Thromboembolic Complications in Cancer Patients" (Authors: Somonova O.V., Antukh E.A., Elizarova A.L., Matveeva I.I., Selchuk V.Yu., Cherkasov V.A., DOI: 10.18 027/2224–5057–2018–8–3s2–604–609, https://rosoncoweb.ru/standarts/RUSSCO/2018/2018-45.pdf).

The principles of prevention and treatment of the consequences of drug extravasation in patients with tracheal cancer correspond to the principles outlined in the guidelines "Recommendations for the Management of Antineoplastic Drug Extravasation Injuries" (Author: Buydenok Yu.V. DOI: 10.18 027/2224–5057–2018–8–3s2–610–616, https://rosoncoweb.ru/standarts/RUSSCO/2018/2018-46.pdf).

The principles of prevention and management of immune-mediated adverse events in patients with tracheal cancer correspond to the principles outlined in the guidelines "Practical Guidelines for the Management of Immune-Mediated Adverse Events" (Authors: Protsenko S.A., Antimonik N.Yu., Bershtein L.M., Novik A.V., Nosov D.A., Petenko N.N., Semenova A.I., Chubenko V.A., Yudin D.I., DOI: 10.18 027/2224–5057–2018–8–3s2–636–665, https://rosoncoweb.ru/standarts/RUSSCO/2018/2018-48.pdf).

4. Medical Rehabilitation and Sanatorium-Resort Treatment

Currently, there are no clinical studies involving patients with tracheal cancer for most types of medical rehabilitation. These recommendations are based on the fact that numerous studies, including meta-analyses (Steffens D. et al., 2018, etc.) and systematic reviews (Stout N.L. et al., 2017; Segal R. et al., 2017, etc.), have proven that various types of medical rehabilitation significantly accelerate functional recovery, shorten postoperative hospital stays, and reduce the incidence of complications and mortality in patients with other malignancies.

4.1 Pre-rehabilitation

4.2 Rehabilitation after surgical treatment

4.2.1 Stage I rehabilitation

4.2.2 Stage II rehabilitation

4.2.3 Stage III rehabilitation

4.3 Rehabilitation after chemotherapy

Comments: This recommendation was developed based on the results of systematic reviews (Nicole L. Stout et al., 2017 and R. Segal et al., 2017) on the impact of physical exercise on patients with other malignant neoplasms.

4.4 Rehabilitation after radiotherapy

4.5 Principles of psychological rehabilitation of patients with malignant neoplasms of the trachea

Comments: in scientific research within psycho-oncology, 3 coping styles are most commonly found among patients with tracheal cancer:

1) active behavioral coping with emotional, physical, and social difficulties associated with the disease and treatment;

2) active-cognitive coping, including attitudes, beliefs, and reflections about the disease;

3) avoidance coping, including attempts to actively avoid problems or indirectly reduce emotional tension through distraction.

Overall, studies show that patients who use active (problem-oriented) survival strategies demonstrate better adaptation to diseases than those who use passive or avoidant survival styles [58].

Patients who used active-behavioral methods of coping with difficulties reported a higher level of self-esteem and energy, fewer physical symptoms, and reduced irritability and asthenia [58].

5. Prevention and Dispensary Observation

Primary prevention of the disease is not available.

• In order to detect disease progression early with the aim of prompt initiation of radiation therapy, chemotherapy, or surgical treatment of resectable metastatic sites and recurrent tumors, all patients after completing treatment for tracheal cancer are recommended to follow the schedule and methods of monitoring below: in the first 1–2 years, physical examination and collection of complaints are recommended every 3–6 months; at 3–5 years, once every 6–12 months.

Scope of examination:

1. Taking medical history and complaints, as well as physical examination.

2. Blood test for carcinoembryonic antigen (if initially elevated) every 3 months for the first 2 years, and then every 6 months for the subsequent 3 years.

3. Tracheobronchoscopy is first performed 3 months after the resection of the primary tumor, then every 3 months for 1 year, then every 6 months during the 2nd year of follow-up, and then once a year or upon the appearance of complaints.

4. Ultrasound of lymph nodes of the cervical-supraclavicular regions (one anatomical region) and abdominal organs (comprehensive) every 3–6 months, depending on the risk of progression.

5. CT of the chest organs with IV bolus contrast enhancement is performed 3 months after the resection of the primary tumor, then every 3 months during the 1st year, then every 6 months during the 2nd year of follow-up, and then once a year or upon the appearance of complaints.

After 5 years from the surgery, visits are conducted annually or upon the appearance of complaints. In patients at high risk of recurrence, the interval between examinations may be shortened [9].

GIB CLOE 4Grade of Recommendation – C (Level of Evidence – 4)

6. Organization of Medical Care

Medical care, with the exception of medical care provided as part of clinical trials, in accordance with Federal Law No. 323-FZ of November 21, 2011 (as amended on May 25, 2019) "On the Fundamentals of Public Health Protection in the Russian Federation", is organized and delivered:

1) in accordance with the regulations on the organization of medical care by types of medical care, which is approved by the authorized federal executive body;

2) in accordance with the procedure for providing care in the profile "oncology", mandatory for implementation on the territory of the Russian Federation by all medical organizations;

3) based on these clinical guidelines;

4) taking into account the standards of medical care approved by the authorized federal executive body.

Primary specialized health care is provided by an oncologist and other medical specialists at an outpatient oncological care center or in a primary oncological office, primary oncological department, or outpatient department of an oncological dispensary.

If an oncological disease is suspected or detected in a patient, general practitioners, district general practitioners, general family practitioners, medical specialists, and mid-level medical personnel shall refer the patient in the established manner for a consultation to an outpatient oncological care center, a primary oncological office, or a primary oncological department of a medical organization to receive primary specialized health-care.

Consultation at an outpatient oncological care center or at a primary oncological office or primary oncological department of a medical organization must be conducted no later than 5 working days from the date of issuance of the referral for consultation. The oncologist of the outpatient oncological care center (in the absence of an outpatient oncological care center, the oncologist of the primary oncological office or primary oncological department) shall organize the collection of biopsy (surgical) material, as well as organize other diagnostic studies necessary to establish the diagnosis, including the extent of the oncological process and the stage of the disease.

In the event that it is impossible to obtain biopsy (surgical) material or perform other diagnostic examinations within the medical organization that houses the outpatient oncological care center (primary oncological office, primary oncological department), the attending physician shall refer the patient to an oncological dispensary or a medical organization providing medical care to patients with oncological diseases.

The timeframe for performing pathological anatomical examinations necessary for the histological verification of a malignant neoplasm must not exceed 15 working days from the date of receipt of the biopsy (surgical) material by the pathological anatomical bureau (department).

If an oncological disease is suspected and/or detected in a patient during the provision of emergency medical care, such patients are transferred or referred to medical organizations providing medical care to patients with oncological diseases to determine management tactics and the need for additional specialized anti-tumor treatment methods.

An oncologist from the outpatient oncology center (primary oncology office, primary oncology department) refers the patient to an oncology dispensary or medical organizations providing medical care to patients with cancer to clarify the diagnosis (if the diagnosis, including the extent of the oncological process and the stage of the disease, cannot be established by the oncologist of the outpatient oncology center, primary oncology office, or primary oncology department) and to provide specialized, including high-tech, medical care.

The timeframe for initiating specialized, excluding high-tech, medical care for cancer patients in a medical organization providing care to cancer patients must not exceed 14 calendar days from the date of histological verification of the malignant neoplasm or 14 calendar days from the date of establishing a preliminary diagnosis of a malignant neoplasm (in the absence of medical indications for pathological anatomical examinations in an outpatient setting).

Specialized, including high-tech, medical care is provided by oncologists and radiation therapists in an oncological dispensary or in medical organizations providing medical care to patients with oncological diseases that have a license, the necessary material and technical base, and certified specialists, in inpatient and day-care settings, and includes the prevention, diagnosis, and treatment of oncological diseases requiring the use of special methods and complex unique medical technologies, as well as medical rehabilitation.

In a medical organization providing medical care to patients with oncological diseases, the tactics of medical examination and treatment are determined by a concilium of oncologists and radiation therapists, involving other specialist physicians if necessary. The decision of the medical concilium is documented in a protocol, signed by the participants of the concilium, and entered into the patient's medical records.

Indications for hospitalization in a medical organization:

1) presence of complications of the oncological disease requiring emergency and urgent specialized medical care (grade II–III respiratory failure, upper respiratory tract bleeding);

2) presence of complications of cancer treatment (surgical intervention, radiation therapy, drug therapy, etc.) that threaten the patient's life;

3) need to perform complex interventional diagnostic medical procedures requiring subsequent monitoring in an inpatient or day hospital setting;

4) presence of indications for specialized antitumor treatment (surgical intervention, radiation therapy, including contact, external beam and other types of radiation therapy, drug therapy, etc.) requiring monitoring in an inpatient or day hospital setting.

Indications for patient discharge from a medical organization:

1) completion of a course of treatment, or one of the stages of specialized, including high-tech, medical care in an inpatient or day hospital setting, provided there are no treatment complications requiring drug correction and/or medical interventions in an inpatient setting;

2) refusal by the patient or their legal representative of specialized (including high-tech) medical care in a round-the-clock or day hospital setting prescribed by the medical board of the oncology care organization, provided there are no complications of the underlying disease and/or treatment requiring drug correction and/or inpatient medical interventions;

3) non-compliance by the patient with prescriptions or internal regulations of the healthcare institution, provided this does not threaten the patient's life or the health of others;

4) need to transfer the patient to another medical organization according to the relevant medical profile.

The conclusion regarding the feasibility of transferring a patient to a specialized medical organization is made after a preliminary consultation based on submitted medical documents and/or a preliminary examination of the patient by medical specialists of the target organization.

7. Additional Information

No additional information available.

Criteria for Evaluating the Quality of Medical Care

References

Appendix A1. Working Group Composition

1. Oleg V. Pikin (Working Group Chair), Doctor of Medical Sciences, Professor, Head of the Thoracic Surgery Department of the Thoracoabdominal Oncology Surgery Division, P.A. Herzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre of the Russian Ministry of Health, member of AOR, ESTS, IASLC.

2. Vitaly V. Barmin, Candidate of Medical Sciences, Associate Professor, Thoracic Surgeon, Head of the Mediastinal and Myasthenia Pathology Center, Head of the Myasthenia Group of the Thoracoabdominal Oncology Surgery Division, P.A. Herzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre of the Russian Ministry of Health, member of AOR, ESTS, IASLC.

3. Andrey V. Vazhenin, Doctor of Medical Sciences, Professor, Academician of the Russian Academy of Sciences, Chief Physician of the Chelyabinsk Regional Clinical Center of Oncology and Nuclear Medicine, member of AOR (Chelyabinsk, Russia).

4. Vyacheslav N. Grinevich, Candidate of Medical Sciences, Head of the Pathomorphology Department of the Outpatient Care Center, P.A. Herzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre of the Russian Ministry of Health.

5. Oksana M. Drapkina, Doctor of Medical Sciences, Professor, Corresponding Member of the Russian Academy of Sciences, Director of the National Medical Research Center for Preventive Medicine of the Russian Ministry of Health.

6. Pavel V. Kononets, Candidate of Medical Sciences, Deputy Director for Scientific and Clinical Work, N.N. Blokhin National Medical Research Center of Oncology of the Russian Ministry of Health, Director of the N.N. Trapeznikov Research Institute of Clinical Oncology.

7. Evgeny V. Levchenko, Doctor of Medical Sciences, Head of the Surgical Thoracic Department, Head of the Scientific Department of Thoracic Oncology, N.N. Petrov National Medical Research Center of Oncology of the Russian Ministry of Health.

8. Irina A. Meshcheryakova, Radiation Oncologist, Candidate of Medical Sciences, Senior Researcher at the Radiation Therapy Department, P.A. Herzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre of the Russian Ministry of Health.

9. Anton V. Snegovoy, Doctor of Medical Sciences, Professor, Head of the Outpatient Chemotherapy Department (Day Hospital), N.N. Blokhin National Medical Research Center of Oncology of the Russian Ministry of Health.

10. Sergey A. Tuzikov, Doctor of Medical Sciences, Professor, Head of the Thoracoabdominal Department of the Oncology Clinic, Tomsk National Research Medical Center of the Russian Academy of Sciences (Tomsk, Russia).

11. Igor N. Turkin, Doctor of Medical Sciences, Head of the Thoracic Surgery Department, Rostov Research Oncological Institute of the Russian Ministry of Health (Rostov-on-Don, Russia).

12. Andrey V. Chernichenko, Doctor of Medical Sciences, Head of the Radiation Therapy Department, P.A. Herzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre of the Russian Ministry of Health.

13. Vladimir D. Chkhikvadze, Doctor of Medical Sciences, Professor, Head of the Department of Surgery and Surgical Technologies in Oncology, Head of the Surgical Clinic, Russian Scientific Center of Roentgenology and Radiology of the Russian Ministry of Health.

14. Konstantin I. Kolbanov, Leading Researcher, Thoracic Surgery Department, Thoracoabdominal Oncology Surgery Division, P.A. Herzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre of the Russian Ministry of Health

15. Aleksandr A. Fedenko, Head of the Drug Treatment of Tumors Department, P.A. Herzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre of the Russian Ministry of Health

16. Larisa V. Bolotina, Head of the Chemotherapy Department, Drug Treatment of Tumors Division, P.A. Herzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Centre of the Russian Ministry of Health

17. Natalya A. Falaleeva, Head of the Drug Treatment of Malignant Neoplasms Division, A.F. Tsyb Medical Radiological Research Centre – branch of the National Medical Research Radiological Centre of the Russian Ministry of Health

18. Elena V. Filonenko, Head of the Center for Laser and Photodynamic Diagnostics and Therapy of Tumors

Medical Rehabilitation and Supportive Care Section:

1. Aleksey V. Butenko, Doctor of Medical Sciences, Professor, Chief Physician of the Research Institute of Clinical Oncology, N.N. Blokhin National Medical Research Center of Oncology of the Russian Ministry of Health, Chair of the Scientific Council "Association of Specialists in Oncological Rehabilitation".

2. Olga A. Okhokhova, Cand. of Sci. (Med.), Senior Research Fellow, Head of the Medical Rehabilitation Department, N.N. Blokhin National Medical Research Center of Oncology of the Russian Ministry of Health, member of the All-Russian Public Organization "Russian Society of Head and Neck Tumor Specialists", member of the European Society for Clinical Nutrition and Metabolism (ESPEN), member of the Russian Society for Parenteral and Enteral Nutrition (RESPEN).

Healthcare Organization Section:

1. Tigran G. Gevorkyan, Deputy Director of the Institute of Clinical and Experimental Radiology, N.N. Blokhin National Medical Research Center of Oncology, Chief Oncologist of the Moscow Region.

2. Sergey A. Ivanov, Dr. of Sci. (Med.), Professor of the RAS, Director of the A.F. Tsyb Medical Radiological Research Center – branch of the National Medical Research Radiological Center of the Russian Ministry of Health.

3. Nevolskikh Alexey Alekseevich, MD, PhD, Deputy Director for Clinical Work, A.F. Tsyb Medical Radiological Research Center – branch of the National Medical Research Radiological Center of the Russian Ministry of Health.

4. Zhanna V. Khaylova, Cand. of Sci. (Med.), Deputy Director for Organizational and Methodological Work, A.F. Tsyb Medical Radiological Research Center – branch of the National Medical Research Radiological Center of the Russian Ministry of Health.

Conflict of interest: none declared by all members of the working group.

Appendix A2. Methodology for Developing Clinical Guidelines

Target audience for these clinical guidelines:

1. Oncologists.

2. Surgeons.

3. Radiologists.

4. Radiation oncologists.

5. Pathologists.

6. Otolaryngologists.

7. Physical and rehabilitation medicine physicians.

8. Clinical pharmacologists.

9. General practitioners.

10. Medical students, residents, and postgraduate students.

In these clinical guidelines, all data are ranked by level of reliability (evidence) depending on the quantity and quality of studies on the issue.

Methods used for evidence collection/selection:

• searching electronic databases;

• analysis of current scientific developments on tracheal cancer in the Russian Federation and abroad;

• summarizing the practical experience of Russian and foreign specialists.

To assess the grades of recommendation (GR) and levels of evidence (LE) for each recommendation thesis, a separate systematic review of the efficacy and/or safety of the medical intervention was performed, including the following stages:

1. Definition of search and selection criteria for publications on clinical trials (CT) regarding the efficacy and/or safety of the medical intervention described in the recommendation statement.

2. Systematic search and selection of clinical trial publications in accordance with predefined criteria.

3. Determination of LTE and GOR based on the results of the systematic search and selection of clinical trial publications.

Methods used for assessing the quality and strength of evidence:

• expert consensus;

• evaluation of LE and GR is carried out based on the standardized scales presented in Tables P1–3.

Table P1. Scale for assessing the level of evidence for diagnostic methods (diagnostic interventions)

Table P2. Scale for assessing the level of evidence for prevention, treatment, and rehabilitation methods (preventive, therapeutic, and rehabilitative interventions)

Table P3. Scale for assessing the grades of recommendation for prevention, diagnostic, treatment, and rehabilitation methods (preventive, diagnostic, therapeutic, and rehabilitative interventions)

Good Practice Points. Good practice recommendations are based on the qualifications and clinical experience of the authoring group.

Methods used for formulating recommendations: expert consensus.

Economic analysis. Cost analysis was not performed, and pharmacoeconomic publications were not reviewed.

Methods of recommendation validation:

• external expert review;

• internal expert review.

Description of the recommendation validation method. The preliminary version of these guidelines was reviewed by independent experts who were asked to comment primarily on whether the interpretation of the evidence underlying the recommendations is easy to understand.

Comments were received from primary care pediatric oncologists regarding the clarity of the guidelines and their perceived importance as a working tool in daily practice.

Comments received from experts were carefully systematized and discussed by the chairman and members of the working group. Each item was discussed, and resulting modifications to the guidelines were recorded. If no changes were made, the reasons for declining the changes were recorded.

Consultations and expert review: the draft guidelines were also reviewed by independent experts who were asked to comment primarily on the clarity and accuracy of the interpretation of the evidence base underlying the guidelines.

For the final editing and quality control, the guidelines were re-analyzed by the members of the working group, who concluded that all comments and feedback from the experts had been taken into account, and the risk of systematic bias in the development of the guidelines was minimized.

Procedure for updating clinical guidelines. The mechanism for updating clinical guidelines provides for their systematic revision at least once every 3 years, as well as upon the emergence of new evidence-based data on the diagnosis, treatment, prevention, and rehabilitation of specific diseases, or in the presence of justified additions/comments to the previously approved clinical guidelines, but no more frequently than once every 6 months.

The decision to update is made by the Russian Ministry of Health based on proposals submitted by medical non-profit professional organizations. The formulated proposals must take into account the results of comprehensive assessments of medicinal products and medical devices, as well as the results of clinical testing.

Appendix A3. Reference Materials

These clinical guidelines have been developed taking into account the following regulatory and legal documents:

1. Order of the Russian Ministry of Health No. 203n dated May 10, 2017, "On Approval of Criteria for Assessing the Quality of Medical Care" (Registered with the Russian Ministry of Justice on May 17, 2017, No. 46740)

2. Order of the Russian Ministry of Health No. 915n of November 15, 2012, "On Approval of the Procedure for Providing Medical Care to Adult Patients with Oncological Diseases".

Current instructions for medicinal products mentioned in these clinical guidelines can be found on the website http://grls.rosminzdrav.ru and on the RUSSCO website.

Appendix B. Physician Action Algorithms

Algorithm for initial diagnosis, examination, and treatment of a patient with a tracheal tumor

Appendix C. Patient Information

Guidelines for post-treatment follow-up

Follow-up after completed treatment is of great importance for maintaining the patient's health. Usually, in the first 1–2 years, follow-up visits with an oncologist are recommended every 1–3 months; in the 2nd year – every 2–6 months; and at 3–5 years – once every 4–8 months. After 5 years from the surgery, visits are conducted annually or upon the appearance of complaints. Nevertheless, the frequency of physician visits may be increased depending on disease characteristics and associated risks and is discussed individually in each specific case. If complaints appear or if symptoms observed before treatment recur, it is necessary to consult a physician immediately without waiting for the scheduled visit date.

The purpose of these visits is to monitor not only the oncological disease but also side effects, including delayed ones (e.g., hypothyroidism after radiation therapy to the neck area, deterioration of nutritional status, assessment of speech and swallowing functions, etc.).

Recommendations regarding lifestyle and nutrition should be individualized taking into account the extent of treatment received, the risks and severity of complications, and the patient's characteristics.

Patients should be informed, depending on indications, about clinical trials conducted in the Russian Federation for patients with the specified disease stage.

Benefits of quitting smoking and alcohol consumption:

1. Higher survival rates.

2. Greater treatment efficacy.

3. Fewer and less severe side effects of antineoplastic treatment (cardiopulmonary complications, fatigue, weight loss, mucositis, loss of taste).

4. Faster recovery of general condition after treatment.

5. Lower risk of recurrence.

6. Lower risk of developing second primary tumors.

7. Lower risk of infections.

8. Higher quality of life.

Recommendations for complications of chemotherapy/chemoradiotherapy/radiotherapy – contact an oncologist (chemotherapy specialist), radiation oncologist!

1) If body temperature rises to 38 °C or higher:

• start taking antibiotics (J01: Antibacterials for systemic use)

• upon the recommendation of an oncologist (chemotherapy specialist).

2) In case of stomatitis:

• diet with mechanical and thermal sparing of the mucosa;

• frequent mouth rinsing (every hour) – chamomile, oak bark, sage, lubricate the mouth with sea buckthorn (peach) oil;

• treat the oral cavity as recommended by an oncologist (chemotherapy specialist).

3) For diarrhea:

• diet – exclude fatty, spicy, smoked, sweet, dairy products, and fiber.

  Lean meat, flour products, fermented dairy products, and rice water are permitted. Drink plenty of fluids;

• take medications as recommended by an oncologist (chemotherapy specialist).

4) For nausea:

• take medications as recommended by an oncologist (chemotherapy specialist).

Appendix G. Assessment Scales, Questionnaires, and Other Evaluation Tools

Appendix G1. WHO/ECOG Performance Status Scale

Russian name: World Health Organization (WHO) / Eastern Cooperative Oncology Group (ECOG) Performance Status Scale.

Original title: The Eastern Cooperative Oncology Group/World Health Organization Performance Status (ECOG/WHO PS).

Source (official developer website, validation publication): https://ecogacrin.org/resources/ecog-performance-status;

Oken M.M., Creech R.H., Tormey D.C. et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol 1982;5(6):649–55 [59].

Type: rating scale.

Purpose: to describe the patient's level of functioning in terms of their ability to care for themselves, daily activities, and physical abilities (walking, work, etc.).

Content (template):

Key (interpretation): Provided within the scale itself.

Appendix G2. Karnofsky Performance Scale

Name in Russian: Karnofsky Scale.

Original name (if any): Karnofsky Performance Status.

Source (official developer website, validation publication):

Karnofsky D.A., Burchenal J.H. The clinical evaluation of chemotherapeutic agents in cancer. In: MacLeod C. (ed.). Evaluation of chemotherapeutic agents. New York: Columbia University Press; 1949:191–205 [60].

Type: rating scale.

Purpose: to describe the patient's level of functioning in terms of their ability to care for themselves, daily activities, and physical abilities (walking, work, etc.).

Content (template):

Key (interpretation): Provided within the scale itself.

Notes: none.

Appendix G3. Response Evaluation Criteria in Solid Tumors (RECIST 1.1)

Russian name: Response Evaluation Criteria in Solid Tumors (RECIST 1.1).

Original name (if any): Response evaluation criteria in solid tumors 1.1.

Source (official developer website, validation publication):

Original publication: Eisenhauer E.A., Therasse P., Bogaerts J. et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer 2009;45(2):228–47 [61].

Type: rating scale.

Purpose: assessment of response to chemotherapy.

The content, key, and template in Russian are presented in methodological recommendations No. 46 of the Scientific and Practical Center for Medical Radiology of the Moscow Healthcare Department and are available on the website http://medradiology.moscow/d/1364488/d/no46_2018_recist_11.pdf.

Appendix G4. Visual Analog Scale for Pain

Name in Russian: Visual Analog Scale for Pain Assessment.

Original name: Visual Analog Scale for Pain (VAS Pain).

Source (official developer website, validation publication):

Original publication: Hawker G.A., Mian S., Kendzerska T., French M. Measures of adult pain: Visual Analog Scale for Pain (VAS Pain), Numeric Rating Scale for Pain (NRS Pain), McGill Pain Questionnaire (MPQ), Short-Form McGill Pain Questionnaire (SF-MPQ), Chronic Pain Grade Scale (CPGS), Short Form-36 Bodily Pain Scale (SF-36 BPS), and Measure of Intermittent and Constant Osteoarthritis Pain (ICOAP). Arthritis Care Res (Hoboken) 2011;63(Suppl 11):S240–52 [62].

Type: rating scale.

Purpose: designed for the quantitative assessment of pain syndrome taking into account the patient's subjective sensations and the selection of analgesic therapy.

Content (template):

“Rate the severity of pain on a scale, where 0 is no pain and 10 is excruciating pain of maximum severity.”

Instructions: the patient is asked to mark the severity of pain on a 10-centimeter line using a scale from 0 to 10.

Key: 1–3 points – mild pain; 4–7 points – moderate pain; 8 points or more – severe pain.

Appendix G5. Verbal Rating Scale for Pain

Russian name: verbal rating scale for pain.

Original name: Verbal Rating/Descriptor Scale.

Source (official developer website, validation publication):

Original publication: Ohnhaus E.E., Adler R. Methodological problems in the measurement of pain: a comparison between the verbal rating scale and the visual analogue scale. // Pain. 1975. Vol. 1, № 4. P. 379–384. [63]

Type: rating scale.

Purpose: designed for the quantitative assessment of pain syndrome taking into account the patient's subjective sensations and the selection of analgesic therapy.

Content (template):

"Rate the severity of pain on a scale from 0 to 10, where 0 is no pain and 10 is the worst imaginable severe pain."

Instructions: the patient answers the question of how they rate the severity of pain on a scale from 0 to 10.

Key: 1–3 points – mild pain; 4–7 points – moderate pain; 8 points or more – severe pain.

Appendix G6. Assessment of tumor regression grade in pathohistological examination using the Mandard system

Russian name: assessment of tumor regression grade in pathohistological examination using the Mandard system.

Original name (if applicable): Mandard scoring system.

Source (official developer website, validation publication):

Mandard AM, Dalibard F, Mandard JC, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic correlations. Cancer. 1994;73(11):2680–2686. doi: 10.1002/1097-0142(19940601)73:11<2680::AID-CNCR2820731105>3.0.CO;2-C [64].

Type: rating scale.

Purpose: reflects the ratio of therapy-induced fibrosis to residual tumor.

Content (template):

Key (interpretation): Provided within the scale itself.

Notes: none.

Appendix G7. Assessment of tumor regression grade in pathohistological examination using the Dworak system

Russian name: assessment of tumor regression grade in pathohistological examination using the Dworak system.

Original name (if applicable): Dworak tumor regression grade.

Source (official developer website, validation publication):

Dworak O., Keilholz L., Hoffmann A. Pathological features of rectal cancer after preoperative radiochemotherapy. Int. J. Colorectal. Dis. 1997;12:19–23. Doi: 10.1007/s003840050072 [65].

Type: rating scale.

Purpose: reflects the ratio of therapy-induced fibrosis to residual tumor.

Content (template):

Key (interpretation): Provided within the scale itself.

Notes: none.