Non-Small Cell Lung Cancer

1. Non-Small Cell Lung Cancer

2. Signs and symptoms • persistent cough • trouble breathing • chest discomfort • wheezing • streaks of blood in sputum • hoarseness • loss of appetite • weight loss for no known reason • feeling very tired

3. Diagnostic tests • chest X-rays • CT, PET scan • sputum cytology • fine-needle aspiration biopsy • bronchoscopy • thoracoscopy • thoracotomy • thoracentesis

4. NSCLC Non-small cell lung cancer (NSCLC) is a heterogeneous aggregate of histologies. The most common histologies are epidermoid or squamous carcinoma, adenocarcinoma, and large cell carcinoma. These histologies are often classified together because approaches to diagnosis, staging, prognosis, and treatment are similar.

5. Cellular Classification • Squamous cell carcinoma • Adenocarcinoma • Large cell carcinoma • Adenosquamous carcinoma. • Carcinomas with pleomorphic, sarcomatoid or sarcomatous elements • Carcinoid tumor • Carcinomas of salivary-gland type • Unclassified carcinoma

6. NSCLC At diagnosis, patients with NSCLC can be divided into 3 groups that reflect both the extent of the disease and the treatment approach

7. NSCLC The first group - tumors that are surgically resectable (generally stage I, stage II, and selected stage III patients). Patients with resectable disease who have medical contraindications to surgery are candidates for curative radiation therapy. Adjuvant cisplatin-based combination chemotherapy may provide a survival advantage to patients with resected stage IB, stage II, or stage IIIA NSCLC.

8. NSCLC The secondgroup includes patients with either locally (T3-T4) and/or regionally (N2-N3) advanced lung cancer. This group has a diverse natural history. • unresectable or N2-N3 disease : radiation therapy in combination with chemotherapy • selected patients with T3 or N2 disease can be treated effectively with surgical resection and either preoperative or postoperative chemotherapy or chemoradiation therapy.

9. NSCLC • final group: metastatic disease (M1) at the time of diagnosis • radiation therapy or chemotherapy for palliation of symptoms from the primary tumor. • platinum-based chemotherapy has been associated with short-term palliation of symptoms and with a survival advantage. • patients previously treated with platinum combination chemotherapy may derive symptom control and survival benefit from docetaxel, pemetrexed, or epidermal growth factor receptor inhibitor.

10. Prognostic determinants after surgery • Presence of pulmonary symptoms. • Large tumor size (>3 cm). • Nonsquamous histology. • Metastases to multiple lymph nodes within a TNM-defined nodal station • Vascular invasion • Increased numbers of tumor blood vessels in the tumor specimen.

11. NSCLC • For patients with inoperable disease, prognosis is adversely affected by poor PS and weight loss of >10%.

12. Stage 0 Non-Small Cell Lung Cancer • Surgical resection using the least extensive technique possible (segmentectomy or wedge resection) to preserve maximum normal pulmonary tissue because these patients are at high risk for second lung cancers. • Endoscopic photodynamic therapy

13. Stage I : T1, N0, M0, T2, N0, M0 Surgery is the treatment of choice -lobectomy or limited resection Patients with inoperable stage I disease and with sufficient pulmonary reserve may be candidates for radiation therapy with curative intent Patients with stage IB disease may benefit from adjuvant platinum-based combination chemotherapy. 5 year OS 27-71%

14. Stage II: T1, N1, M0; T2, N1, M0; T3, N0, M0 • Lobectomy; pneumonectomy; or segmental, wedge, or sleeve resection as appropriate. • Radiation therapy with curative intent (for potentially operable patients who have medical contraindications to surgery). • Adjuvant chemotherapy with or without other modalities after curative surgery • 5 year OS 10-60%

15. Stage IIIA T1-2 N2; T3 N1-2 • Surgery alone in operable patients without bulky lymphadenopathy. • Radiation therapy alone, for patients who are not suitable for neoadjuvant chemotherapy plus surgery. • Chemotherapy combined with other modalities. • 5 year OS 2-28%

16. Stage IIIB Any T, N3, M0; T4, any N, M0 • initial chemotherapy, chemotherapy plus radiation therapy, or radiation therapy alone, depending on the sites of tumor involvement and their performance status (PS). • patients with malignant pleural effusion are rarely candidates for radiation therapy and should generally be treated similarly to stage IV patients. • A meta-analysis of patient data from 11 randomized clinical trials showed that neoadjuvant or concurrent cisplatin-based combinations plus radiation therapy resulted in a 10% reduction in the risk of death compared with radiation therapy alone.

17. Stage IV Any T, any N, M1 • External-beam radiation therapy, primarily for palliative relief of local symptomatic tumor growth. • Cisplatin- based chemotherapy.

18. SCLC • Without treatment, small cell carcinoma of the lung has the most aggressive clinical course of any type of pulmonary tumor, with median survival from diagnosis of only 2 to 4 months. • Compared with other cell types of lung cancer, small cell carcinoma has a greater tendency to be widely disseminated by the time of diagnosis but is much more responsive to chemotherapy and irradiation.

19. SCLC • With incorporation of current chemotherapy regimens into the treatment program, survival is prolonged, with at least a 4- to 5-fold improvement in median survival compared with patients who are given no therapy. • The overall survival at 5 years is 5% to 10%.

20. Cellular Classification • Small cell carcinoma. • Mixed small cell/large cell carcinoma. • Combined small cell carcinoma (i.e., small cell lung cancer combined with neoplastic squamous and/or glandular components).

21. Limited-stage disease • tumor confined to the hemithorax of origin, the mediastinum, and the supraclavicular nodes, which can be encompassed within a tolerable radiation therapy port. No universally accepted definition of this term is available, and patients with pleural effusion, massive pulmonary tumor, and contralateral supraclavicular nodes have been both included within and excluded from limited stage by various groups.

22. Extensive-stage disease • Extensive-stage small cell lung cancer means tumor that is too widespread to be included within the definition of limited-stage disease above. Patients with distant metastases (M1) are always considered to have extensive-stage disease

23. Prognostic factors • good performance status, female gender, and limited-stage disease • patients with involvement of the central nervous system or liver at the time of diagnosis have a significantly worse outcome

24. Limited-Stage Small Cell Lung Cancer- treatment • Combination chemotherapy with chest irradiation: EC: etoposide + cisplatin + 4,500 cGy chest radiation therapy • Combination chemotherapy especially in patients with impaired pulmonary function or poor performance status. • Surgical resection followed by chemotherapy or chemotherapy plus chest radiation therapy • PCI prophylactic cranial irradiation

25. Limited-Stage Small Cell Lung Cancer • combination chemotherapy is superior to single-agent treatment, • current programs yield overall objective response rates of 65% to 90% and complete response rates of 45% to 75% • because of the frequent presence of occult metastatic disease, chemotherapy is the cornerstone of treatment for patients with limited-stage small cell lung cancer.

26. Limited-Stage Small Cell Lung Cancer • combined modality therapy produces significant improvement in survival compared with chemotherapy alone • two meta-analyses showed an improvement in 3-year survival rates of about 5% for those receiving chemotherapy and radiation therapy compared with those receiving chemotherapy alone. Most of the benefit occurred in patients younger than 65 years.

27. Combined modality treatment • Studies strongly suggest that minimal tumor doses in the range of 4,000 cGy to 4,500 cGy or more (standard fractionation) are necessary to effectively control tumors in the thorax.

28. Combined modality treatment • median survivals: 18 to 24 months and 40% to 50% 2-year survival with <3% treatment-related mortality • once-daily and twice-daily chest radiation schedules have been used in regimens with etoposide and cisplatin. • One randomized study showed a modest survival advantage in favor of twice-daily radiation therapy given over 3 weeks, compared with once-daily radiation therapy given over 5 weeks (26% vs. 16% at 5 years, P = .04).

29. Limited-Stage Small Cell Lung Cancer • Combined modality treatment is associated with increased morbidity and, in some trials, increased treatment-related mortality from pulmonary and hematologic toxic effects; proper administration requires close collaboration between medical and radiation oncologists

30. PCI prophylactic cranial irradiation • Patients whose cancer can be controlled outside the brain have a 60% actuarial risk of developing central nervous system metastases within 2 to 3 years after starting treatment. The majority of these patients relapse only in their brain, and nearly all of those who relapse in their central nervous system die of their cranial metastases

31. PCI- prophylactic cranial irradiation • Patients who have achieved a complete remission can be considered for prophylactic cranial irradiation (PCI).

32. PCI prophylactic cranial irradiation • The risk of developing central nervous system metastases can be reduced by >50% by the administration of PCI in doses of 2,400 cGy • a meta-analysis of 7 randomized trials evaluating the value of PCI reported improvement in brain recurrence, disease-free survival, and overall survival with the addition of PCI. The 3-year overall survival was improved from 15% to 21% with PCI.

33. PCI • The majority of patients with small cell lung cancer have neuropsychological abnormalities present before the start of cranial irradiation and have no detectable decline in their neurological status for as long as 2 years after the start of their cranial irradiation

34. Extensive-Stage Small Cell Lung Cancer • Combination chemotherapy with one of the following regimens with or without PCI given to patients with complete responses: -CAV: cyclophosphamide + doxorubicin + vincristine. -CAE: cyclophosphamide + doxorubicin + etoposide. -EP or EC: etoposide + cisplatin or carboplatin. -ICE: ifosfamide + carboplatin + etoposide. -Cisplatin + irinotecan • irradiation reserved for nonresponding patients

35. Skin cancer • Basal cell carcinoma • squamous cell carcinoma • Although these 2 types of skin cancer are the most common of all malignancies, they account for <0.1% of patient deaths due to cancer.

36. Skin cancer • Both of these types of skin cancer are more likely to occur in individuals of light complexion who have had significant exposure to sunlight, and both types of skin cancer are more common in the southern latitudes of the Northern hemisphere.

37. Basal Cell Carcinoma of the Skin • Mohs micrographic surgery- the tumor is microscopically delineated until it is completely removed. Indications: • tumors with poorly defined clinical borders; • tumors with diameters >2 cm; • tumors with histopathologic features showing morpheaform or sclerotic patterns; • tumors arising in regions where maximum preservation of uninvolved tissue is desirable, such as eyelid, nose, finger, and genitalia. • cure rates have been reported at 96%

38. Basal Cell Carcinoma of the Skin • Simple excision- tumor recurrence is not uncommon because only a small fraction of the total tumor margin is examined pathologically. Recurrence rate for primary tumors >1.5 cm in diameter is at least 12% within 5 years; if the primary tumor measures >3 cm, the 5-year recurrence rate is 23.1%. Primary tumors of the ears, eyes, scalp, and nose have recurrence rates ranging from 12.9% to 25%.

39. Basal Cell Carcinoma of the Skin • Electrodesiccation and curettage. This method is the most widely employed method for removing primary basal cell carcinomas. Although it is a quick method for destroying the tumor, adequacy of treatment cannot be assessed immediately since the surgeon cannot visually detect the depth of microscopic tumor invasion.

40. Basal Cell Carcinoma of the Skin • Cryosurgery- may be considered for patients with small, clinically well-defined primary tumors. It is especially useful for debilitated patients with medical conditions that preclude other types of surgery.

41. Basal Cell Carcinoma of the Skin • Radiation therapy: for patients with primary lesions requiring difficult or extensive surgery (e.g., eyelids, nose, or ears) • Cosmetic results are generally good to excellent with a small amount of hypopigmentation or telangiectasia in the treatment port. • Radiation therapy can also be used for lesions that recur after a primary surgical approach.

42. Squamous Cell Carcinoma of the Skin • Localized squamous cell carcinoma of the skin is a highly curable disease.The traditional methods of treatment involve the use of cryosurgery, radiation therapy, electrodesiccation and curettage, and simple excision. • Of all treatment methods available, Mohs micrographic surgery has the highest 5-year cure rate for both primary and recurrent tumors. • Lymphadenectomy is indicated when regional lymph nodes are involved.

43. Melanoma malignum • most melanomas arise in the skin, they may also arise from mucosal surfaces or at other sites to which neural crest cells migrate • Melanoma occurs predominantly in adults, and more than 50% of the cases arise in apparently normal areas of the skin

44. Prognosis • Thickness and/or level of invasion of the melanoma, mitotic index, presence of tumor infiltrating lymphocytes, number of regional lymph nodes involved, and ulceration or bleeding at the primary site affect the prognosis. • Patients who are younger, female, and who have melanomas on the extremities generally have a better prognosis.

45. Prognosis • For disease clinically confined to the primary site, the greater the thickness and depth of local invasion of the melanoma, the higher the chance of lymph node or systemic metastases and the worse the prognosis

46. Stage Clark’s classification (level of invasion)TNM definitionsClinical stagingAJCC stage groupingsPathologic stagingAJCC stage groupings

47. Melanoma malignum • localized melanoma: surgical excision with margins proportional to the microstage of the primary lesion • melanomas that have spread to regional lymph nodes may be curable with excision of the primary tumor and removal of the involved lymph nodes

48. Melanoma malignum • adjuvant high-dose interferon was shown to increase relapse-free and overall survival when compared to observation • adjuvant chemotherapy does not improve survival

49. Patients with distant metastasis • Treatment in clinical trials: • combination chemotherapy • biological response modifiers (such as specific monoclonal antibodies, interferons, IL-2, or tumor necrosis factor-alfa), vaccine immunotherapy, or chemoimmunotherapy.

50. Recurrent Melanoma • Resection of isolated single or localized metastases from skin, visceral, or brain sites in selected patients is sometimes associated with prolonged survival. • Palliative radiation therapy for bone, spinal cord, or brain metastases. • Palliative biologic therapy and/or chemotherapy in phase I and II clinical trials. • Palliative treatment with interleukin-2 or interferon can occasionally result in prolonged survival. • Isolated hyperthermic limb perfusion for extremity recurrences.