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Non-Small Cell Carcinoma Lung, Role of Radiation therapy after surgery.
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Nsclc port
- 2. Lung cancer is the most common cancer worldwide and accounts for the most cancer-related deaths. Non–small cell lung cancers (NSCLC) account for over 80% of all cases; the rates of small cell lung cancers (SCLC) fall with the reduction in smoking rates.
- 3. RISK FACTORS Smoking. Asbestos exposure. Foundry workers & welders: Ni, Co, Cd. Uranium mine workers: Inhaled Radon gas. Air pollution: Diesel exhaust, Metal fumes, Air Sulfate & PAH content.
- 4. NON SMALL CELL LUNG CANCER (80%) ADENOCARCINOMA (35%) Most common cell type overall Most common in women Most common cell type in non-smokers but still most patients are smokers Peripheral SQUAMOUS CELL CARCINOMA (30%) Strongly associated with smoking Most common carcinoma to cavitate Poor prognosis LARGE CELL CARCINOMA (15%) Peripherally located Very large, usually more than 4 cm.
- 5. ESMO
- 6. TNM STAGING (AJCC 8th)
- 16. 8thEd.
- 18. Role of Radiotherapy Radiotherapy role in Non-Small Cell Lung Cancer Can be Definitive Adjuvant Palliative Aim of Modern Radiotherapy is To maximize Tumor control. To minimize Treatment toxicity. Minimum technological standard is 3DCRT. More advanced include 4D-CT, PET/CT simulation, IMRT/VMAT/IGRT, motion management and proton therapy.
- 19. Early stage NSCLC (Stage I & selected node negative stage IIA): SBRT is recommended for patients who are medically inoperable or who refuse to have surgery. SBRT achieved primary control rates and overall survival comparable to lobectomy and higher than 3D-CRT in comparable medically inoperable and older patients. In patients treated with surgery, port is not recommended unless there are positive margins or upstaging to N2.
- 20. Locally advanced NSCLC (stage II-III): Concurrent ChemoRadiotherapy is recommended for patients with inoperable stage II(node positive) and stage III NSCLC . Sequential CRT or RT alone is appropriate for frial patients unable to tolerate concurrent therapy. Pre-operative concurrent CRT is an option for patients with resectable stage IIIA (minimal N2 and treatable with lobectomy). resectable superior sulcus tumors.
- 21. Advanced/Metastatic NSCLC (stageIV): RT is recommended for local palliation or prevention of symptoms like pain, bleeding, or obstruction. Definitive local therapy to oligometastasis to achieve prolonged survival in a small proportion of well selected patients with good preformance status who have received radical therapy to the intrathoracic disease.
- 23. POST OPERATIVE RADIOTHERAPY (PORT) Concern over locoregional failure led to the idea that PORT in completely resected stages II and IIIA NSCLC might be beneficial because of evidence that it reduced local recurrence. Before 1998 more than 50% patients operated were offered PORT. However, the ROLE OF PORT CALLED INTO QUESTION in 1998 when the Medical Research Council published a meta-analysis of nine randomized controlled trials assessing the effect of PORT after resection.
- 24. PORT Meta-analysis Trialists Group (1998) 9 trials of surgery alone vs post-op RT. 2,128 patients. 24% reduction in local recurrences. For pN0–1 patients, PORT produced a 7% absolute OS decrement. (2yr reduced OS from 55% to 48%) 21% relative increase in the risk of death with RT (1,368 deaths). Adverse effects was greatest for Stage I,II. There was no survival difference for pN2 patients.
- 25. This analysis has been criticized for many reasons Twenty-five percent of the patients were pN0 who did not need adjuvant therapy. Treatment with cobalt-60 teletherapy units was allowed in 7 of the 9 trials. There was no quality control in the radiotherapy arms, and it was felt to be inferior to modern standards. Suboptimal Radiation techniques like lateral radiation beam designs and relatively large radiation fields. 4 trials used relatively large daily radiation fractionation schedules [> 2 grays (Gy) per day]
- 26. These techniques increased normal tissue toxicity lead to deleterious consequences in a population of patients with already compromised cardiac and pulmonary reserve. A sub-study by Dautzenberg et al (1999) reveled 31% deaths in PORT arm are cardiac and respiratory deaths.
- 28. • Improved survival may be secondary to improvements in the treatment planning and delivery of thoracic radiotherapy
- 32. Subsequent studies that investigated the role of PORT
- 34. In this study by Lally et al, over 7,465 patients with stage II/III resected NSCLC were evaluated. On multivariate analysis, older age, T3-4 tumor stage, N2 node stage, male sex, fewer sampled lymph nodes, and greater number of involved lymph nodes had a negative impact on survival. The use of PORT did not have a significant impact on survival. BUT…
- 35. Subset analysis for patients with N2 nodal disease (hazard ratio [HR] 0.855; 95% CI, 0.762 to 0.959; P .0077), PORT was associated with a significant increase in survival. (5-year OS- 27 vs 20%) For patients with N0 (HR 1.176; 95% CI, 1.005 to 1.376; P .0435) and N1 (HR 1.097; 95% CI, 1.015 to 1.186; P .0196) nodal disease, PORT was associated with a significant decrease in survival.
- 39. • Scotti et al, Retrospective study with 175 patients from 1988 to 2004, resected NSCLC stages IIIA-IIIB, N2 disease. Significant reduction in local recurrence (LR) in PORT group (32% vs 15%) (log-rank test p = 0.015; HR: 0.45; 95%CI: 0.24– 0.87). No statistical difference were found in terms of overall survival (OS) (log-rank test p = 0.92).
- 41. PORT data from the ANITA trial Douillard JY et al, re-analysis of PORT data from phase III adjuvant chemo trial (THE ADJUVANT NAVELBINE INTERNATIONAL TRIALIST ASSOCIATION (ANITA) RANDOMIZED TRIAL) Stages IB–IIIA patients treated with adjuvant Cisplatin and Vinorelbine versus observation , with or without PORT (232 of 840 patients received PORT) As a group, PORT was detrimental on survival (HR = 1.34)
- 42. Subset analysis based on pN stage showed PORT was For pN0 – detrimental In pN1 Improved survival in observation arm (12% survival advantage of PORT in the no adjuvant chemotherapy arm ) Detrimental for adjuvant chemotherapy arm.(16% survival disadvantage in the arm receiving adjuvant chemotherapy) For pN2 patients, PORT improved survival for both observation and chemotherapy arms.
- 44. CONCLUSION In patients with clinical stage I/II upstaged surgically to N2+ PORT appears to improve survival significantly as an adjuvant to post operative chemo therapy. PORT is not recommended for patients with pathological stage N0-1 disease, because it has been associated with increased mortality, at least when using older RT techniques.
- 45. THANK YOU
- 47. Guidelines for treatment of NSCLC
Editor's Notes
- Occupational & Environmental exposure
- This includes an assessment by the pulmonologist and operating surgeon of the clinical extent of disease, the predicted postresection pulmonary reserve of the patient, and preoperative cardiac clearance for the intended surgical procedure. Although there are no strict guidelines for operability, traditionally patients are considered to be suitable for pneumonectomy if their predicted postoperative forced expiratory volume in 1 second (FEV1) is >1.2 L. Additional contraindications to pneumonectomy are hypercarbia and cor pulmonale. Patients are usually referred for preoperative pulmonary function testing, including spirometry, diffusion capacity, and arterial blood gases. Imaging studies include ventilation-perfusion imaging to determine the regional variance in pulmonary function, including the potential loss of functional lung tissue within the planned area of excision.
- 7% absolute increase in mortality associated with PORT, despite a 24% reduction in local recurrences. Given the theoretical benefit of radiotherapy on local control, the detriment in survival was attributed to excessive radiotherapy-induced morbidity exceeding any benefit.
- . This analysis has been criticized for many reasons. Twenty-five percent of the patients were pN0 who did not need adjuvant therapy. There was no quality control in the radiotherapy arms, and it was felt to be inferior to modern standards; many of the patients were treated to large volumes using older Cobalt-60 equipment to fields designed under fluoroscopy. both of these techniques have been associated with increased normal tissue toxicity.
- THE ADJUVANT NAVELBINE INTERNATIONAL TRIALIST ASSOCIATION (ANITA) RANDOMIZED TRIAL 232 OF 840 patients received PORT
- PORT is generally administered after post op chemo, PORT with concurrent chemo can be given in medically fit patients and is recommended for positive resection margins.
- RT has a poten of nsclc as either definitive palliative Critical role of modern RT are to maximise tomor control and to minimize treatment toxicity. Minimum technological standard is 3DCRT More advanced include 4dct pet/ct simulation, imrt/vmat/igrt, motion management and proton therpy Early stage nsclc Stage I selected node nagative stage Iia: SBRT is recommended for patients who are medically inoperable or who refuse to have surgery. SBRT achieved primary control rates and overall survival compareble to lobectromy and higher than 3dcrt in comparable medically inoperable and older patients. In patients treated with surgery, port is not recommended unless there are positive margins or upstaging to N2 Locally advanced nsclc stage II-III: Concurrent crt is recommended for patients with inoperable stage II(node positive) and stage III nsclc followed by consolidation durvalumab for stageIII Sequential crt or rt alone is appropriate for frial patients unable to tolerate concurrent therapy. Role of rt pre-post operative. Preop concurrent crt is an option for patients with resectable stage IIIA(minimal N2 and treatable with lobectomy) and is recommended for resectable superior sulcus tumors. Pre-op And post op rt is an alterative for patients with resectable In patients with clinical stagwe I/II upstafged surgically to N2+, PORT appears to improve survival significantly as an adjuvant to post operative chemo therapy in non rndomised analysis. PORT is generally administered after post op chemo, PORT with concurrent chemo can be given in medicallt fit patients and is recommended for positive resection margins. PORT is not recommended for patients with pathological stage N0-1 disease, because it has been associated with increased mortality, at least when using older rt techniques. Advanced/Metastatic NSCLC (stageIV): RT is recommended for local palliation or prevention of symptoms like pain, bleeding, or obstruction. Definitive local therapy to oligomets to achieve prolonged survival in a small proportion of well selected patients with good preformance status who have received radical therapy to the intrathoracic disease.