IIIB Non-small Cell Lung Carcinoma Research Articles

Low Prognostic Nutritional Index Predicts Poor Clinical Outcomes in Patients with Stage IIIB Non-small-cell Lung Carcinoma Undergoing Chemoradiotherapy.

PurposeTo investigate the prognostic utility of the prognostic nutritional index (PNI) in stage IIIB non-small-cell lung carcinoma (NSCLC) patients undergoing concurrent chemoradiotherapy (CRT).MethodsA total of 358 stage IIIB NSCLC patients who received a total dose of 60–66 Gy (2 Gy/fraction) radiotherapy and ≥1 cycle(s) of platinum-based chemotherapy were analyzed. The receiver operating curve analysis was utilized to identify the optimal PNI cut-off value demonstrating a significant connection with the overall survival (OS), locoregional progression-free survival (LRPFS), and progression-free survival (PFS).ResultsAt a median follow-up time of 22.5 months (range: 2.4–123.5), 30.2% and 14% of the patients were still alive and free of disease progression, respectively.The median OS, LRPFS, and PFS were 25.2 [95% confidence interval (CI): 36.3–46.6 months], 15.4 (95% CI: 26.6–35.3 months), and 10.7 (95% CI: 36.8–69.9 months), individually, for the whole study accomplice. The ROC analysis revealed an optimum rounded cut-off that associated meaningfully with each of the OS [area under the curve (AUC): 84.1%; sensitivity: 75.9%;72.4% specificity], LRPFS (AUC: 92.4%; sensitivity: 87.9%; 85.1% specificity), and PFS (AUC: 80.1%; sensitivity: 73.7%; 71.6% specificity) at a value of 40.5. Comparative analyses revealed that the patients presenting with PNI≤40.5 had significantly inferior OS (16.8 vs 36.7; P<0.001), LRPFS (11.5 vs 19.5; P<0.001), and PFS (8.6 vs 13.6; P<0.001) outcomes compared to patients with PNI>40.5. In univariate analyses, lower T-stage (1–2 vs 3–4; P< 0.001), lower N-stage (N2 vs N3; P< 0.001), anemia status (absent vs present; P< 0.001), weight loss status (<5% vs ≥5%; P< 0.001), and PNI group (≤40.5 vs >40.5; P<0.001) were the factors found to be associated with OS, LRPFS and PFS results. The results of multivariate analysis exhibited that the PNI was independently associated with each of the OS (P<0.001), LRPFS (P<0.001), and PFS (P<0.001) outcomes.ConclusionThe pretreatment PNI appears to be a robust novel prognostic factor that stratifies patients with stage IIIB NSCLC into two significantly distinct survival groups after CRT.

Implantation of computed tomography-guided Iodine-125 seeds in combination with chemotherapy for the treatment of stage III non-small cell lung cancer.

PurposeWe investigated the role of computed tomography (CT)-guided Iodine-125 (125I) seed implantation in combination with chemotherapy for the treatment of stage III non-small cell lung carcinoma (NSCLC).Material and methodsThe data from 182 patients with stage III NSCLC who were treated with radioactive 125I seed implantation between June 2002 and June 2009, and who received sequential platinum-based combination chemotherapy using the most common combination of platinum and gemcitabine, were retrospectively reviewed. The 182 patients received a prescribed dose of 110.0 Gy, with a median radioactivity of 0.70 mCi (range, 0.64-0.78 mCi, 2.37-3.26 × 107 Bq). The median number of 125I seeds was 38 pellets (range, 6-105 pellets). The median post-operation dose covering 100% of the target volume (D100) was 94.5 Gy (range, 54.6-125.5 Gy). The median D90 was 143.0 Gy (range, 121.6-184.0).ResultsThe 1-, 3-, and 5-year overall survival rates were 83.35%, 25.57%, and 11.34%, respectively; the median survival time was 24.76 months. At 1, 3, and 5 years, the local control rates were 92.01%, 86.51%, and 76.45%, respectively; the median local control time was 25.28 months. For patients with stage IIIA and IIIB NSCLC, the median survival times were 26.67 and 24.59 months, respectively (p = 0.2). Pre-treatment hemoglobin level, tumor volume, and postoperative D100 were significantly associated with survival. A total of 24 patients experienced pneumothorax (incidence rate, 13.20%), and 17 patients experienced hemothorax (incidence rate, 5.0%).ConclusionsCT-guided 125I seed implantation combined with chemotherapy is an effective, minimally invasive method for the treatment of stage III NSCLC. Furthermore, hemoglobin levels before treatment, D100, and the maximum diameter of the tumor may be prognostic factors in patients with NSCLC treated sequentially with radiotherapy and chemotherapy.

Outcomes of aggressive concurrent radiochemotherapy in highly selected septuagenarians with stage IIIB non-small cell lung carcinoma: Retrospective analysis of 89 patients

We retrospectively evaluated the toxicity and efficacy of concurrent radiochemotherapy (C-RCT) in medically fit septuagenarians with stage IIIB non-small cell lung carcinoma (NSCLC). Eighty-nine medically fit, stage IIIB NSCLC septuagenarians were included. Thoracic radiotherapy to a total dose of 66Gy in 2Gy fractions was delivered concurrently with 1–2 cycles of cisplatin-based doublet chemotherapy. Treatment was relatively well-tolerated with no grade 4/5 acute toxicity. Acute grade 3 hematologic and non-hematologic toxicity rates were 55.1 and 39.3%, respectively. Late toxicity was reported in 3 (3.4%) patients: esophagitis (N=2) and peripheral neuropathy (N=1). At median 21.7 months (4.4–42.1), 26 patients (29.2%) were alive. Median overall, local-regional progression-free and progression-free survivals were 17.7, 10.5 and 7.8 months, respectively. On univariate analyses, histology (p<0.03), nodal status (p=0.038), number of concomitant chemotherapy (p<0.001), and weight change during C-RCT (p<0.001) demonstrated significant association with overall survival; while only number of chemotherapy and weight change (p<0.001 for each) could retain their significance on multivariate analyses. Current results suggested that C-RCT in highly selected medically fit septuagenarians with LA-NSCLC may improve survival outcomes up to that achieved in younger patients, with a relatively acceptable toxicity profile.

Influence of oral glutamine supplementation on survival outcomes of patients treated with concurrent chemoradiotherapy for locally advanced non-small cell lung cancer

BackgroundGlutamine (Gln) supplementation during concurrent chemoradiotherapy (C-CRT) effectively reduces the incidence and severity of acute radiation-induced esophagitis (RIE). However, there are concerns that Gln might stimulate tumor growth, and therefore negatively impact the outcomes of anticancer treatment. We retrospectively investigated the effect of co-administration of oral Gln during C-CRT on survival outcomes of patients with stage IIIB non-small cell lung carcinoma (NSCLC). We additionally evaluated role of oral Gln in preventing C-CRT-induced weight change, acute and late toxicities.MethodsThe study included 104 patients: 56 (53.8%) received prophylactic powdered Gln (Gln+) orally at a dose of 10 g/8 h and 48 (46.2%) did not receive Gln (Gln-) and served as controls. The prescribed radiation dose to the planning target volume was 66 Gy in 2-Gy fractions. Primary endpoints of progression-free survival (PFS), local/regional progression-free survival (LRPFS), and overall survival (OS) were correlated with status of Gln supplementation.ResultsOral Gln was well tolerated except for mild nausea/vomiting in 14 (25.0%) patients. There was no C-CRT-related acute or late grade 4–5 toxicity. Administration of Gln was associated with a decrease in the incidence of grade 3 acute radiation-induced esophagitis (RIE) (7.2% vs. 16.7% for Gln+ vs. Gln-; p=0.02) and late-RIE (0% vs. 6.3%; p=0.06), a reduced need for unplanned treatment breaks (7.1% vs. 20.8%; p=0.04), and reduced incidence of weight loss (44.6% vs. 72.9%; p=0.002). At a median follow-up of 24.2 months (range 9.2-34.4) the median OS, LRPFS, and PFS for Gln+ vs. Gln- cohorts were 21.4 vs. 20.4 (p=0.35), 14.2 vs.11.3 (p=0.16), and 10.2 vs. 9.0 months (p=0.11), respectively.ConclusionIn our study, supplementation with Gln during C-CRT had no detectable negative impact on tumor control and survival outcomes in patients with Stage IIIB NSCLC. Furthermore, Gln appeared to have a beneficial effect with respect to prevention of weight loss and unplanned treatment delays, and reduced the severity and incidence of acute- and late-RIE.

1202P - Outcomes of Aggressive Concurrent Chemotherapy in Septuagenarians with Stage IIIB Non-Small Cell Lung Carcinoma

ABSTRACT Background Aim of the study was to retrospectively assess the feasibility of radical chemoradiotherapy in terms of tolerability and survival outcomes in medically fit 71 to 79 years old stage IIIB NSCLC patients. Materials and methods From the hospital records, 78 medically fit, septuagenerians with stage IIIB lung carcinoma were evaluated. Patients should have performance of ECOG 0-1, body mass index of ≥20kg/m2, and weight loss of Results Patients characteristics are given in Table 1 . All patients received planned 66 Gy TRT but 55 of them (70.5%) could receive 2 cycles of chemotherapy. In general, treatment was well-tolerated with no grade 4/5 acute toxicity. Late term toxicity was reported in 3 (3.8%); esophagitis in 3 and peripheral neuropathy in 1 patient. At a median follow up of 19.3 months (4.4-39.8), 19 patients (24.4%) were alive, 8 of whom (10.3%) were with no disease progression. Median overall, local-regional progression-free and progression-free survival were 17.5 (95%CI: 15.2-19.8), 10.1 (95% CI: 7.8-12.4) and 7.3 months (95% CI: 5.9-8.9). On univariate analyses, histology (p = 0.017), Nodal status (p = 0.011), number of concomitant CT (p Age Median 74.4 (71 – 79) Sex Male Female 51 (65.4) 27 (34.6) Performance status ECOG 0 ECOG 1 38 (48.7) 40 (51.3) Histology SCC Adeno 43 (55.1) 35 (44.9) Stage T2N3 T3N3 T4N2 T4N3 15 (19.2) 22 (28.2) 28 (35.9) 13 (16.7) Conclusion Results present here suggests that CRT in highly selected medically fit septuagenarians with LA-NSCLC yields survival outcomes improved up to that achieved in younger patients, with a relatively acceptable toxicity profile. Table 1 Disclosure All authors have declared no conflicts of interest.

Spontaneous haemopericardium with subacute cardiac tamponade in a patient with lung cancer receiving coumadin

A 74-year-old woman with a history of stage IIIb non-small cell lung carcinoma undergoing concomitant chemoradiation therapy presented to the emergency centre with a 2-day history of dyspnea and chest tightness. The patient had a pulmonary embolism 1 month earlier, because of which she was receiving a therapeutic dosage of coumadin. On physical examination, she was …

Results of a phase I dose‐escalation study using three‐dimensional conformal radiotherapy in the treatment of inoperable nonsmall cell lung carcinoma

The objective of this study was to report the results of a Phase I dose-escalation study using three-dimensional conformal radiation therapy (3D-CRT) for the treatment of patients with nonsmall cell lung carcinoma (NSCLC). Between 1991 and 2003, 104 patients were enrolled for 3D-CRT at Memorial Sloan-Kettering Cancer Center. The median patient age was 69 years. Twenty-eight percent of patients had Stage I-II NSCLC, 33% of patients had Stage IIIA NSCLC, 32% of patients had Stage IIIB NSCLC, and 6% of patients had recurrent NSCLC. Induction chemotherapy was received by 16% of patients. Radiation was delivered in daily fractions of 1.8 grays (Gy) for doses < or = 81.0 Gy and in daily fractions of 2.0 Gy for higher doses. Accrual at a dose level was complete when 10 patients received the intended dose without unacceptable acute morbidity. After an incident of fatal acute radiation pneumonitis at the starting dose of 70.2 Gy, the protocol was modified to limit normal tissue complication probabilities (NTCP) to < 25%. The dose was then escalated from 70.2 Gy, to 75.6 Gy, 81.0 Gy, and 84.0 Gy, with at least 10 patients treated at each dose level. Unacceptable pulmonary toxicity occurred at 90.0 Gy. Subsequently, another 10 patients were accrued at the 84.0 Gy level with acceptable toxicity. Thus, 84.0 Gy was the maximum tolerated dose (MTD). The crude late pulmonary toxicity rate was 7%, the 2-year local control rate was 52%, the disease-free survival rate was 33%, and the overall survival rate was 40%. The median survival was 21.1 months. Overall survival was improved significantly in patients who received > or = 80.0 Gy. The MTD of 3D-CRT for NSCLC with an NTCP constraint of 25% was 84.0 Gy in the current study. There was a suggestion of improved survival in patients who received 80.0 Gy.

Influence of tumor volume on survival in patients irradiated for non—small-cell lung cancer

Purpose: To investigate the importance of CT-defined total tumor volume (TTV) on overall survival (OS) in patients with unresectable or medically inoperable non—small-cell lung carcinoma (NSCLC).Methods and Materials: Between 1991 and 1998, 150 evaluable patients with Stage I—IIIB NSCLC were treated with three-dimensionally planned conformal radiotherapy and curative intent at Duke University Medical Center. On the treatment-planning CT, the primary tumor and nodal volumes were identified and subsequently combined to form the TTV. The TTV was compared with the stage and outcome with respect to OS, local progression-free survival, and distant failure-free survival using the Kruskall—Wallis analysis of variance and Kaplan—Meier actuarial method. To account for the potentially confounding effects of therapeutic and patient-specific covariates on survival, the Cox proportional hazard regression model was used.Results: The TTVs in patients with Stage I disease (median 19 cm3) were smaller than in patients with Stage II (median 80 cm3) or Stage III (median 97 cm3; p <0.001) disease. The Stage II TTVs were not significantly different from those of Stage III (post-hoc test according to Bonferroni). Prolonged OS was independently associated with a small TTV (<80 vs. >80 cm3 [median]; p = 0.01), young age (<60 vs. ≥60 years; p = 0.03), high Karnofsky performance status (≤70 vs. >70; p = 0.04), and female gender (p = 0.04). Both stage (p = 0.7) and T stage (p = 0.06) were of less importance for OS than was the TTV, according to multivariate modeling. Increased local progression-free survival (p = 0.001) and distant failure-free survival (p = 0.03) were independently associated with a small TTV (i.e., <80 cm3). The results were unchanged if the TTV was analyzed as a continuous variable.Conclusion: A strong independent association between a small CT-defined TTV and prolonged survival in patients with NSCLC selected for curative/definitive RT was found. Future therapeutic studies in NSCLC should consider stratifying/adjusting for differences in TTV to avoid confounding effects on survival from variations in the TTV at baseline.

Is lung cancer surgery justified in patients with direct mediastinal invasion?

To assess the results of the surgical treatment of patients with stage IIIB non-small cell lung carcinoma (NSCLC) invading the mediastinum (T4). Twenty-nine patients were operated on from 1986 to 1999. Histology was squamous cell carcinoma in 17 patients, adenocarcinoma in eight, large cell carcinoma in two and neuroendocrinal carcinoma in two. Three patients received a preoperative chemotherapy (n = 2) or radiochemotherapy (n = 1). The lung resection consisted of a pneumonectomy in 25 patients and a lobectomy in four. The procedure was extended to one of the following structures: superior vena cava (SVC) (n = 17), aorta (n = 1), left atrium (n = 5) and carina (n = 6). Seventeen patients had a postoperative regimen including radiochemotherapy (n = 12), radiotherapy (n = 4), or chemotherapy (n = 1). Complete R0 resection was achieved in 25 patients, whereas four patients had a microscopically (n = 1) or macroscopically (n = 3) residual disease. The operative mortality rate was 7% (n = 2). Non-fatal major complications occurred in eight patients (28%). Overall 5-year survival rate was 28% (median 11 months), including the operative mortality. The median survival of the 18 patients with an N0 or N1 disease was 16 months whereas the median survival of the 11 patients with an N2 disease was 9 months. At completion of the study, 22 patients have died, two postoperatively and 10 from pulmonary causes without evidence of cancer. Surgical management of T4 NSC lung cancer invading the mediastinum should be considered, in the absence of N2 disease, when a complete resection is achievable.

Flexible chemotherapy regimen with gemcitabine and vinorelbine for metastatic nonsmall cell lung carcinoma

This Phase II study evaluated a flexible 3- or 4-week dosing schedule of gemcitabine and vinorelbine to determine its effect on response rate and survival of patients with metastatic nonsmall cell lung carcinoma (NSCLC). Thirty-four response-evaluable patients, 24 with performance status (PS) 0-1 and 10 with a PS of 2, 30 with Stage IV, and 4 with Stage IIIB NSCLC were treated with gemcitabine 1000 mg/m(2) intravenously and vinorelbine 25 mg/m(2) intravenously (first 15 patients) or 30 mg/m(2) intravenously (next 19 patients) on Days 1, 8, and 15 of a 4-week cycle, if on Day 15 neutrophils were > or = 1500/uL and platelets > or = 100,000/uL. If chemotherapy could not be administered on Day 15, then Day 22 became Day 1 of the next cycle. When vinorelbine 25 mg/m(2) was given with gemcitabine 1000 mg/m(2), 11 patients received 4-week cycles, 3 patients 3-week cycles, and 1 patient both 3- and 4-week cycles. With vinorelbine 30 mg/m(2) and gemcitabine 1000 mg/m(2), 7 patients received 4-week cycles, 2 patients 3-week cycles, and 10 patients both 3- and 4-week cycles. The partial response rate for 34 patients was 53% (18 patients). Median survival (MS) was 11.1 months, and 1-year survival 50% (17 patients). Patients with PS 0+1 had a MS of 17.5 months compared with patients with PS 2, who had MS of 3.3 months. Patients < 70 years of age had a MS of 18 months, and those >/= 70 years had a MS of 5.5 months. This flexible schedule with gemcitabine and vinorelbine enabled optimal dose delivery and suggested excellent efficacy but less toxicity than treatment with platinum regimens.

Is prolonged survival possible for patients with supraclavicular node metastases in non-small cell lung cancer treated with chemoradiotherapy?: analysis of the radiation therapy oncology group experience

Purpose: To determine if patients with non-small cell lung carcinoma (NSCLC) and positive supraclavicular nodes (SN+) have a similar outcome to other patients with Stage IIIB NSCLC (SN−) when treated with modern chemoradiotherapy. Methods and Materials: Using the Radiation Therapy Oncology Group (RTOG) database, data were retrospectively analyzed from five RTOG trials studying chemoradiotherapy for NSCLC: 88-04, 88-08 (chemo-RT arm), 90-15, 91-06, 92-04. Comparisons were made between the SN+ and SN− subgroups with respect to overall survival, progression-free survival (PFS), and metastases-free survival (MFS) using the log rank test. Cox multivariate proportional hazards regression analysis was used to determine the effect of several potential confounding variables, including histology (squamous vs. nonsquamous), age (>60 vs. ≤60), Karnofsky Performance Status (KPS) (<90 vs. ≥90), weight loss (≥5% vs. <5%), and gender. Results: A total of 256 Stage IIIB patients were identified, of whom 47 had supraclavicular nodes (SN+) and 209 did not (SN−). Statistically significantly more SN+ patients had nonsquamous histology ( p = 0.05); otherwise, known prognostic factors were well balanced. The median survival for SN+ patients was 16.2 months, vs. 15.6 months for SN− patients. The 4-year actuarial survival rates were 21% and 16% for SN+ and SN− patients respectively ( p = 0.44). There was no statistically significant difference in the 4-year PFS rates (19% vs. 14%, p = 0.48). The Cox analysis did not show the presence or absence of supraclavicular nodal disease to be a prognostic factor for survival, MFS, or PFS. The only statistically significant factor on multivariate analysis was gender, with males having a 40% greater risk of mortality than females ( p = 0.03). There were no clinically significant differences in toxicity when comparing SN+ vs. SN− patients. Among the 47 SN+ patients, there were no reported cases of brachial plexopathy or other ≥ Grade 2 late neurologic toxicity. Conclusions: When treated with modern chemoradiotherapy, the outcome for patients with supraclavicular metastases appears to be similar to that of other Stage IIIB patients. SN+ patients should continue to be enrolled in trials studying aggressive chemoradiotherapy regimens for locally advanced NSCLC.

A phase I/II trial of neoadjuvant chemotherapy with cisplatin and vinorelbine followed by accelerated irradiation for patients with inoperable nonsmall cell lung carcinoma

Both locoregional and distant disease control remains poor in the treatment of Stage III nonsmall cell lung carcinoma (NSCLC). This trial was conducted to evaluate the tolerance and responses of patients with NSCLC given a neoadjuvant regimen of cisplatin and vinorelbine chemotherapy followed by accelerated thoracic radiotherapy. Forty-two patients with Stage IIIA and IIIB NSCLC were entered into the study. Treatment consisted of cisplatin 100 mg/m2 given on Days 1 and 29 and vinorelbine 30 mg/m2 given weekly for 5 weeks, with a planned 50% dose reduction to 15 mg/m2 planned for Week 2. This was followed by thoracic irradiation of 60 gray (Gy) in 30 fractions of 2 Gy over 4 weeks (once daily during Weeks 1 and 2 and twice daily during Weeks 3 and 4). With a median follow-up time of 12.2 months (27-65 months for survivors), the median survival was 12.2 months (16.6 months for patients with no prior weight loss and 7.8 months for those with prior weight loss). The response rate after induction chemotherapy was 46.1%, increasing to 74.4% after radiation therapy (8 complete responses and 21 partial responses). The rate of progression was 13 of 18 (72%) for those who responded to chemotherapy (4 distant, 9 local) and 18 of 21 (86%) for those who did not respond to chemotherapy (14 distant, 7 local). The most frequent acute Grade 3 toxicity was nausea (21.4%). Accelerated thoracic irradiation after induction chemotherapy is well tolerated and yields therapeutic results that compare favorably with those reported for other regimens of chemotherapy and standard fractionated radiotherapy. The data from this study suggest that the responses of patients with clinically apparent disease to induction chemotherapy might indicate a likelihood of controlling microscopic distant metastases.

The possible advantage of hyperfractionated thoracic radiotherapy in the treatment of locally advanced nonsmall cell lung carcinoma

BACKGROUND A three-arm Phase III randomized trial was performed to compare response rates, time to local or distant progression, and survival for patients with unresectable (Stage IIIA or IIIB) nonsmall cell lung carcinoma treated with standard fractionated thoracic radiotherapy (SFTRT) versus accelerated hyperfractionated thoracic radiotherapy (AHTRT) with or without combination etoposide and cisplatin chemotherapy. METHODS This trial was initiated in 1992 by the North Central Cancer Treatment Group. Patients with Stage IIIA or IIIB nonsmall cell lung carcinoma were eligible. They were randomly assigned to either SFTRT (6000 centigray [cGy] in 30 fractions) or AHTRT (150 cGy twice daily to a total dose of 6000 cGy, with a 2-week break after the initial 3000 cGy); the AHTRT was given alone or with concomitant cisplatin (30 mg/m2, Days 1-3 and 28-30) and etoposide (100 mg/m2, Days 1-3 and 28-30). RESULTS A total of 110 patients were entered on study. Eleven patients were declared ineligible or off study on the day of study entry. This analysis was confined to the 99 eligible patients. This article reports mature follow-up, because more than 80% of the patients have died. The median follow-up of living patients was 2.5 years. There were suggestions of improvement in the rates of freedom from local recurrence and survival for patients treated with AHTRT (with or without chemotherapy) as opposed to SFTRT (P = 0.06 and P = 0.10, respectively). The improvement in survival associated with AHTRT (with or without chemotherapy) was statistically significant for the subgroup of patients with nonsquamous cell carcinoma after adjustment for other potentially confounding factors (P = 0.02). No differences in freedom from systemic progression or survival were found in a comparison of AHTRT with chemotherapy and AHTRT without chemotherapy. CONCLUSIONS These results suggest that treatment of Stage IIIA or IIIB nonsmall cell lung carcinoma with AHTRT with or without chemotherapy may improve freedom from local progression and survival as compared with SFTRT, especially for patients with nonsquamous cell carcinoma. The statistical powers to detect the observed differences in median time to local progression and survival were approximately 55% and 35%, respectively. Therefore, further investigation comparing SFTRT with AHTRT is warranted. Cancer 1998;82:1037-48. © 1998 American Cancer Society.

The possible advantage of hyperfractionated thoracic radiotherapy in the treatment of locally advanced nonsmall cell lung carcinoma

A three-arm Phase III randomized trial was performed to compare response rates, time to local or distant progression, and survival for patients with unresectable (Stage IIIA or IIIB) nonsmall cell lung carcinoma treated with standard fractionated thoracic radiotherapy (SFTRT) versus accelerated hyperfractionated thoracic radiotherapy (AHTRT) with or without combination etoposide and cisplatin chemotherapy. This trial was initiated in 1992 by the North Central Cancer Treatment Group. Patients with Stage IIIA or IIIB nonsmall cell lung carcinoma were eligible. They were randomly assigned to either SFTRT (6000 centigray [cGy] in 30 fractions) or AHTRT (150 cGy twice daily to a total dose of 6000 cGy, with a 2-week break after the initial 3000 cGy); the AHTRT was given alone or with concomitant cisplatin (30 mg/m2, Days 1-3 and 28-30) and etoposide (100 mg/m2, Days 1-3 and 28-30). A total of 110 patients were entered on study. Eleven patients were declared ineligible or off study on the day of study entry. This analysis was confined to the 99 eligible patients. This article reports mature follow-up, because more than 80% of the patients have died. The median follow-up of living patients was 2.5 years. There were suggestions of improvement in the rates of freedom from local recurrence and survival for patients treated with AHTRT (with or without chemotherapy) as opposed to SFTRT (P = 0.06 and P = 0.10, respectively). The improvement in survival associated with AHTRT (with or without chemotherapy) was statistically significant for the subgroup of patients with nonsquamous cell carcinoma after adjustment for other potentially confounding factors (P = 0.02). No differences in freedom from systemic progression or survival were found in a comparison of AHTRT with chemotherapy and AHTRT without chemotherapy. These results suggest that treatment of Stage IIIA or IIIB nonsmall cell lung carcinoma with AHTRT with or without chemotherapy may improve freedom from local progression and survival as compared with SFTRT, especially for patients with nonsquamous cell carcinoma. The statistical powers to detect the observed differences in median time to local progression and survival were approximately 55% and 35%, respectively. Therefore, further investigation comparing SFTRT with AHTRT is warranted.

Concurrent carboplatin, etoposide and thoracic radiation for poor-risk Stage III non-small-cell lung carcinoma: A pilot study

A pilot study was conducted to assess the tolerance and efficacy of concurrent carboplatin, etoposide, and thoracic radiation in poor-risk patients with Stage III non-small-cell lung carcinoma (NSCLC). Patients had Stages IIIA/IIIB NSCLC and were ineligible for available clinical trials employing cisplatin-based chemoradiation due to one or more protocol-defined poor-risk factors or concomitant medical conditions. Treatment consisted of thoracic radiation, 1.8 to 2 Gy daily, to the primary tumor and regional lymph nodes to a total dose of 61 Gy. Concurrently, patients received carboplatin 200 mg/m2/day intravenously on days 1, 3, 29, and 31, and etoposide 50 mg/m2/day intravenously on days 1-4 and 29-32. Response was assessed by chest computed tomography (CT) 4 weeks after treatment was completed. A total of 26 patients were enrolled and 23 of these patients, including 11 with Stage IIIA and 12 Stage IIIB NSCLC, were eligible and assessable. Ninety-six percent (96%) of the patients completed the two planned courses of chemotherapy, and 87% completed the planned chest radiation. Grade III/IV toxicities included neutropenia in nine patients (39%), thrombocytopenia in five (22%), esophagitis in seven (30%), and nausea in two (9%). One patient died of a pulmonary embolism during treatment, and another died of complications due to a tracheoesophageal fistula. Four patients (17%) achieved a complete response and 16 (70%) a partial response, yielding an overall response rate of 87%. The median survival was 12 months, and the 2-year actuarial survival was 40%. This treatment regimen was well tolerated, with promising response and survival in poor-risk patients with Stage III NSCLC. These results are being validated in a Phase II trial conducted by the Southwest Oncology Group.

Chemoradiation enhances response in stage IIIB lung cancer

Upon workup, the vast majority of non-small cell lung cancer patients are unresectable. Classically these patients undergo external beam radiation alone to 6,000 cGy which results in a disappointing 8.9 month median survival and high local failure rate. To enhance response, radiation dose was escalated and combined with multiagent chemotherapy for patients with stage IIIB non-small cell lung carcinoma. Eight patients (ages 54–75 years, mean 63 years) were initiated on CT guided radiation therapy to the primary tumor, mediastinum, and ipsilateral supraclavicular fossa to 5,400 cGy in 200 cGy/day fractions. The primary tumor bed was then boosted to 7,400 cGy at 200 cGy/day. Concomitant with the radiation boost 4–6 monthly cycles of Cisplatinum and VP16 were initiated in an outpatient setting. Diflucan and Carafate were dispensed to minimize mucositis during radiation therapy. All eight patients completed the prescribed treatment course without interruption. No patient was hospitalized due to treatment-related toxicity and mucositis was minimal. At 12 month follow-up each patient was alive without pulmonary complaint and radiographically none had disease progression at the primary site. Four patients developed evidence of metastatic disease: one at 4 months (brain), the second at 9 months (brain), the third at 12 months (bone), and the fourth at 18 months (contralateral lung). Overall, median survival was 24 months (range 15–40 months). In conclusion, dose escalation of radiation with concomitant chemotherapy offers excellent pulmonary palliation without undue morbidity. Local control and survival appear to be increased compared to radiation alone but further evaluation is required in larger trials. Radiat Oncol Invest 1996;4:171–175. © 1996 Wiley-Liss, Inc.