Tag Archives: adjuvant radiotherapy

Treatment of Stage IIIA Non-small Cell Lung CancerPotentially Resectable N2 Disease

6. Induction (Neoadjuvant) Therapy: Patients with stage IIIA (N2) lung cancer identified preoperatively have a relatively poor prognosis when treated with surgery as a single modality. Several small trials of induction chemotherapy have yielded conflicting results about its effect on survival. The relative roles of surgery and radiation therapy as the local treatment modality are also not clearly defined. Definitive treatment recommendations are difficult to make in this setting. Therefore, patients in this subset should be referred for multidisciplinary evaluation before embarking on definitive treatment. Level of evidence: poor; benefit: none; grade of recommendation: I
7. Induction (Neoadjuvant) Therapy: Whenever possible, induction (neoadjuvant) therapy followed by surgery for stage IIIA disease should be carried out in the setting of a clinical trial. Level of evidence: fair; benefit: moderate; grade of recommendation: B

Treatment of Stage IIIA Non-small Cell Lung Cancer: Summary of Recommendations

Treatment of Stage IIIA Non-small Cell Lung Cancer: Summary of RecommendationsDespite many earlier studies, the optimal treatment recommendations in the various clinical presentations of stage IIIA (N2) disease are unclear. Hopefully, as the current phase III trials accrue and mature and the much-needed, subsequent randomized trials with newer chemotherapy agents and radiotherapy schemata are started and completed, more definitive treatment guidelines will emerge. Until that time, it is critically important that whenever possible the clinician who manages locally advanced NSCLC enroll their patients in every available clinical trial.
A. Incidental (Occult) N2 Disease Found at Thoracotomy
1. Surgical Consideration: In patients with an occult single-station mediastinal node metastasis that is recognized at thoracotomy and when a complete resection of the nodes and primary tumor is technically possible, then proceed with the planned lung resection and a mediastinal lymphadenectomy. Level of evidence: poor; benefit: small; grade of recommendation: C canadian health&care mall

2. Surgical Consideration: In every patient undergoing a lung resection for lung cancer, systematic mediastinal lymph node sampling or complete mediastinal lymph node dissection must be performed. Level of evidence: good; benefit: substantial; grade of recommendation: A

Treatment of Stage IIIA Non-small Cell Lung Cancer: Combination Chemotherapy and Radiotherapy

B. Neoadjvuant (Induction) Therapy Phase III Randomized Trials in Resectable Stage IIIA
North American Intergroup 0139: This trial compares concurrent combination chemotherapy with cisplatin and etoposide plus radiotherapy followed by surgery or radiotherapy in stage IIIA (N2) disease (completed accrual and now closed).
EORTC 08941: A European study comparing platinum-based chemotherapy of choice followed (in responders only) by surgery or radiotherapy.

Treatment of Stage IIIA Non-small Cell Lung Cancer: Ongoing Clinical Trials

Treatment of Stage IIIA Non-small Cell Lung Cancer: Ongoing Clinical TrialsPerhaps the greatest challenge to the clinician in the optimal management of stage IIIA disease is the lack of meaningful, definitive data from large randomized trials on which to base treatment decisions.
A large number of phase I and II trials are accruing involving locally advanced disease with newer chemotherapy agents, newer radiotherapy delivery techniques and fractionation schedules, and novel interventions such as vaccines and gene-based therapy. Fortunately, a number of large, multicenter phase III randomized trials are also ongoing, and on completion should provide results that serve as the basis for rationale treatment recommendations in the various clinical presentations of stage IIIA disease.

Treatment of Stage IIIA Non-small Cell Lung Cancer: unresectable IIIA (N2) disease

Newer-generation chemotherapeutic agents, alone or in combination with the platinum agents, are being incorporated into combined modality chemotherapy plus radiotherapy for locally advanced disease. As an example, a recent phase II trial in locally advanced disease used induction paclitaxel with carboplatin followed by weekly doses concurrent with radiotherapy. This treatment yielded a good response rate (55%) in 38 evaluable patients, with a 1-year survival of 72% and a tolerable toxicity profile.
Other phase I and II trials have reported the feasibility of combining docetaxel, gemcitabine, and irino-tecan in concurrent design with radiotherapy but also do report a range of toxicity profiles. Phase III trials are needed that incorporate these newer, active agents in various dosing schedules with radiotherapy in standard and altered fractionation schedules to define the optimal role of these agents in treatment strategies for unresectable IIIA (N2) disease.

Treatment of Stage IIIA Non-small Cell Lung Cancer: Chemotherapy plus radiotherapy

Treatment of Stage IIIA Non-small Cell Lung Cancer: Chemotherapy plus radiotherapyConcurrent Chemotherapy and Radiotherapy: Concurrent chemotherapy with radiotherapy has been studied in the locally advanced setting through randomized trials that have attempted to capitalize on the radiosensitizing properties of chemotherapy. An EORTC three-arm trial published in 1992 compared radiotherapy (split course) concurrent with daily or weekly concurrent cisplatin to radiotherapy alone. There were improved 2-year and 3-year survivals for daily chemotherapy concurrent with radiotherapy compared with radiotherapy alone (26% and 16% vs 13% and 2%, respectively). There was no significant advantage for the weekly chemo-therapy-plus-radiotherapy arm, with an intermediate survival compared to the other arms.

Treatment of Stage IIIA Non-small Cell Lung Cancer: PS-2 patients

The superiority of combined-modality chemotherapy plus radiotherapy in a sequential fashion compared to radiotherapy alone has been shown in several other large randomized trials including a Radiation Therapy Oncology Group trial showing an improved 1-year and median survival with chemotherapy plus conventional radiotherapy compared to both conventional radiotherapy and hyperfractionated radiotherapy alone. A multicenter French study reported by Le Chevalier and associates also confirmed improved survival for the chemotherapy-plus-radiotherapy arm compared to radiotherapy alone (11% vs 5% 3-year survival, respectively) with an improved distant failure rate for chemotherapy plus radiotherapy (22% vs 46% at 1 year, respectively).

Treatment of Stage IIIA Non-small Cell Lung Cancer: CALGB

Treatment of Stage IIIA Non-small Cell Lung Cancer: CALGBIn general, trials using platinum-containing chemotherapy regimens in combination with radiotherapy have shown good tumor response rates and have suggested an improvement in survival. One promising pilot trial showed significantly improved median and 2-year survivals of 16 months and 30%, respectively, using four cycles of etoposide and cisplatin with concurrent radiotherapy to 60 Gy. Looking at collective data from multiple phase II trials, acute and late toxicities associated with combined chemotherapy and radiotherapy have included mild-to-severe esophagitis, pneumonitis, and also treatment-related deaths. Overall, however, these trials showed the feasibility of combined modality therapy and suggested that chemotherapy plus radiotherapy would yield improved outcomes compared to radiotherapy alone.

Treatment of Stage IIIA Non-small Cell Lung Cancer: ECOG

A recent Eastern Cooperative Oncology Group (ECOG) pilot study (ECOG 4593) utilized this schedule and obtained a preliminary median survival of 13 months with acceptable toxicities, primarily esophagitis, at the completion of radiother-apy. In a subsequent companion quality-of-life assessment of patients undergoing the accelerated HART regimen in EGOG 4593, Auchter and asso-ciates found that the decrement in physical and functional quality of life during treatment returned to baseline within 4 weeks of completing treatment. However, the emotional well-being of patients improved at all time points.

Treatment of Stage IIIA Non-small Cell Lung Cancer: CHART

Treatment of Stage IIIA Non-small Cell Lung Cancer: CHARTRadiotherapy Alone: Early attempts to use non-surgical treatment modalities for unresectable locally advanced disease (our stage IIIA4) involved single modality chest radiotherapy, yielding poor survivals at 5 years of 5 to 10% with traditional dose and fractionation schedules (1.8 to 2.0 Gy per fraction per day to 60 to 70 Gy in 6 to 7 weeks). Patterns of failure for patients treated with radiotherapy alone included both locoregional and distant failures. Attempts to improve on locoregional control tested alternative radiotherapy doses and schedules, applying radiotherapy at escalating doses at shortened intervals (hyperfractionation) that, in theory, would maximize cell killing in lung cancers with relatively short doubling times.

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