Stage IIIA-IIIB Non-small Cell Lung Cancer Research Articles

Molecular imaging research on 18F-FDG PET/CT and biomarker analysis to predict the efficacy of neoadjuvant camrelizumab combined with chemotherapy for resectable stage IIIA-IIIB NSCLC.

e15065 Background: The purpose of this study was to explore the predictive value of tumor and secondary lymphoid metabolic parameters on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and circulating biomarkers for pathological response of neoadjuvant camrelizumab combined with chemotherapy in patients with non-small cell lung cancer (NSCLC). Methods: We included 22 patients who was diagnosed with NSCLC (stage IIIA-IIIB (T3-4N2)) and underwent curative surgery after receiving 3 cycles of camrelizumab plus chemotherapy between January 2023 and January 2024 in Shandong Cancer Hospital. Radical surgery was performed within 4-6 weeks after neoadjuvant therapy. Patients undergo 18F-FDG PET/CT scans in 1 week before treatment and 1 week before surgery. Pathological outcomes were assessed and divided into pathologic complete response (pCR) and non-pCR (defined as residual tumor > 0%). The PET/CT parameters were measured, including tumor metabolic parameters such as maximum normalized uptake value (SUVmax), average normalized uptake value (SUVmean), total pathological glycolysis (TLG), and metabolic tumor volume (MTV). Additionally, secondary lymphoid organ metabolic parameters like the spleno-liver SUVmax ratio (SLR) and bone marrow-liver SUVmax ratio (BLR) were assessed. Furthermore, lymphocyte subsets and inflammatory biomarkers in peripheral blood were analyzed. The correlation between PET/CT metabolic parameters, lymphocyte subsets, inflammatory biomarkers and pathological response was analyzed. Results: pCR was achieved in 8 of the 22 patients. SUVmax in both pCR (p<0.001) and non-pCR patients (p<0.001) decreased before surgery. Among patients with pCR, the absolute value of decreased SUVmax (p = 0.024) and the rate of decreased SUVmax (ΔSUVmax%) (p = 0.042) before surgery was higher than those in non-pCR patients. In pCR group, SLR has a decreasing trend before surgery (p = 0.083). In circulating biomarker analysis, the percentage of NK cells changes (ΔNK%) of patients with pCR before surgery was higher than that of patients with non-pCR (p = 0.029). Neutrophil-to-lymphocyte ratio (NLR) in pCR group decreased significantly (p = 0.021) before surgery and there also had declining trend in the non-pCR group (p = 0.062). Before surgery, systemic immune-inflammation index (SII) was significantly decreased in both pCR (p = 0.028) and non-pCR (p<0.001) groups. There also had significant decrease in derived neutrophil-to-lymphocyte ratio (dNLR) before surgery in both pCR (p = 0.01) and non-pCR (p = 0.031) groups. Conclusions: The SUVmax of the primary site at baseline, ΔSUVmax% and ΔNK% have good value in pCR for patients with stage IIIA-IIIB NSCLC receiving neoadjuvant camrelizumab combined with chemotherapy. More analysis of biomarkers is ongoing.

Video-Assisted Thoracoscopic Surgery Versus Thoracotomy Following Neoadjuvant Immunochemotherapy in Resectable Stage III Non-Small Cell Lung Cancer Among Chinese Populations: A Multi-Center Retrospective Cohort Study

BackgroundImmune checkpoint inhibitors have revolutionized non-small cell lung cancer (NSCLC) treatment but may pose greater technical challenges for surgery. This study aims to assess the feasibility and oncological effectiveness of video-assisted thoracoscopic surgery (VATS) for resectable stage III NSCLC after neoadjuvant immunochemotherapy. MethodsInitial stage IIIA-IIIB NSCLC patients with neoadjuvant immunochemotherapy undergoing either VATS or open lobectomy at 6 medical centers during 2019-2023 were retrospectively identified. Perioperative outcomes and 2-year survival was analyzed. Propensity-score matching (PSM) was employed to balance patient baseline characteristics. ResultsAmong the total 143 patients, PSM yielded 62 cases each for VATS and OPEN groups. Induction-related adverse events were comparable between the 2 groups. VATS showed a 14.5% conversion rate. Notably, VATS decreased numeric rating scales for postoperative pain, shortened chest tube duration (5[4-7] vs. 6[5-8] days, P = .021), reduced postoperative comorbidities (21.0% vs. 37.1%, P = .048), and dissected less N1 lymph nodes (5[4-6] vs. 7[5-9], P = .005) compared with thoracotomy. Even when converted, VATS achieves perioperative outcomes equivalent to thoracotomy. Additionally, over a median follow-up of 29.5 months, VATS and thoracotomy demonstrated comparable 2-year recurrence-free survival (77.20% vs. 73.73%, P = .640), overall survival (87.22% vs. 88.00%, P = .738), cumulative incidences of cancer-related death, and recurrence patterns. Subsequent subgroup comparisons and multivariate Cox analysis likewise revealed no statistical difference between VATS and thoracotomy. ConclusionVATS is a viable and effective option for resectable stage III NSCLC patients following neoadjuvant immunochemotherapy, leading to decreased surgical-related pain, earlier chest tube removal, reduced postoperative complications, and similar survival outcomes compared to thoracotomy.

Enhancing Patient Selection in Stage IIIA-IIIB NSCLC: Invasive Lymph Node Restaging after Neoadjuvant Therapy.

Restaging of mediastinal lymph nodes plays a crucial role in the multimodal treatment of stage IIIA Non-Small-Cell Lung Cancer (NSCLC). This study aimed to assess the impact of restaging using endobronchial ultrasound (EBUS), endoesophageal ultrasound (EUS), and transcervical extended mediastinal lymphadenectomy (TEMLA) after neoadjuvant chemotherapy (CHT) or chemoradiotherapy (CRT) on the 5-year overall survival (OS) of patients with NSCLC diagnosed with clinical stage IIIA-IIIB and metastatic ipsilateral mediastinal nodes (N2) who underwent radical pulmonary resections. Patients diagnosed with stage IIIA-IIIB NSCLC and N2 mediastinal nodes were included in this study. Restaging of mediastinal lymph nodes was performed using EBUS, EUS, and TEMLA. The patients were divided into two groups based on the restaging method: the TEMLA restaging group and the chest CT scan-only group. The primary outcome measure was the 5-year OS rate, and the secondary outcome measures included median OS and survival percentages. Statistical analysis, including the log-rank test, was conducted to assess the differences between the two groups. The TEMLA restaging group demonstrated significantly better overall survival compared to the chest CT scan-only group (log-rank test, p = 0.02). This was evident through a four-fold increase in median OS (59 vs. 14 months) and a higher 5-year OS rate of 55.9% (95% CI: 40.6-71.1) compared to 25.0% (95% CI: 13.7-36.3) in the chest CT scan-only group (p = 0.003). Invasive restaging of mediastinal lymph nodes improves the selection of patients with stage IIIA-IIIB (N2) NSCLC after neoadjuvant therapy. The use of EBUS, EUS, and TEMLA provides valuable information for identifying patients who may benefit from surgery by identifying N2 to N0-1 downstaging. These findings emphasize the importance of incorporating restaging procedures into the treatment decision-making process for NSCLC patients with mediastinal lymph node involvement.

The prognostic value of RDW, NLR and PLR in sequential radio-chemotherapy for advanced lung cancer

Introduction.Inflammation plays an important role in carcinogenesis, therefore morphology-based inflammatory indi­ces could be prognostic factors in lung cancer patients. This study aimed to analyze if red cell distribution width (RDW), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) are associated with patients’ prognosis in non-small cell lung cancer (NSCLC) patients. Material and methods.The study population included 110 patients treated with definitive sequential radio-chemo­therapy for stage IIIA–IIIB NSCLC. The data were retrospectively analyzed using the receiver operating characteristic (ROC) method, Kaplan-Meier estimator, log-rank testing, and Cox proportional hazards regression model. Results.The ROC analysis has shown that the optimal cut-off values were 14% for RDW, 2.1 for NLR, and 120 for PLR, with area under the curve (AUC) of 0.606, 0.509, and 0.564 respectively. The overall survival was significantly higher in patients with RDW ≤ 14% with a median survival of 31.2 months compared to 20.2 months for patients with RDW > 14%. RDW was an independent prognostic factor in multivariate analysis. Conclusions.RDW can provide additional information in assessing patients’ prognosis, but it is necessary to consider its modest sensitivity and specificity. NLR and PLR were not found to be independent prognostic factors.

The prognostic value of pre-treatment thrombocytosis in two cohorts of patients with non-small cell lung cancer treated with curatively intended chemoradiotherapy.

Chemoradiotherapy is the standard of care for inoperable stage III non-small cell lung cancer (NSCLC). This treatment, however, offers only a small chance of cure and is associated with many side effects. Little research has been made concerning which patients benefit most/least from the treatment. The present study evaluates the prognostic value of anemia, leukocytosis and thrombocytosis at diagnosis in this treatment setting. In the present study, data were collected retrospectively for 222 patients from two different phase II studies conducted between 2002-2007 in Sweden with patients treated with chemoradiotherapy for stage IIIA-IIIB NSCLC. Clinical data and the serum values of hemoglobin (Hgb), White blood cells (WBC) and Platelets (Plt) at enrollment were collected for all patients and studied in relation to overall survival using Kaplan-Meier product-limit estimates and a multivariate Cox proportional hazards regression model. The results showed that patients with thrombocytosis (Plt > 350 x 109/L) had a shorter median overall survival (14.5 months) than patients with normal Plt at baseline (23.7 months). Patients with leukocytosis (WBC > 9 x 109/L) had a shorter median survival (14.9 months) than patients with a normal WBC at baseline (22.5 months). However, in a multivariate model including all lab parameters and clinical factors, only thrombocytosis and performance status displayed a prognostic significance. In Conclusion, thrombocytosis showed to be an independent prognostic marker associated with shorter overall survival in stage III NSCLC treated with curatively intended chemoradiotherapy. This knowledge can potentially be used together with established prognostic factors, such as performance status when choosing the optimal therapy for the individual patient in this clinical setting.

Phase II Study of Concurrent Pemetrexed, Cisplatin, and Radiation Therapy for Stage IIIA/B Unresectable Non–Small Cell Lung Cancer

IntroductionConcurrent thoracic radiation and platinum-based chemotherapy is the standard of care for treatment of unresectable stage IIIA-IIIB non–small-cell lung cancer (NSCLC), but the optimal drug regimen has not been established. Patients and MethodsIn the present single-arm phase II trial, patients with previously untreated, unresectable stage IIIA-IIIB NSCLC (all histologic types) were treated with pemetrexed-cisplatin (500 mg/m2 intravenously on days 1 and 22, 20 mg/m2 intravenously on days 1-5 and days 22-26) concurrent with radiotherapy (61-66 Gy in 31-35 fractions), followed by 2 cycles of consolidation pemetrexed-cisplatin (75 mg2) therapy. The primary endpoint was the 1-year overall survival (OS) rate. The study treatment was considered active if the 1-year OS rate was ≥ 70%. ResultsA total of 39 patients, including 6 from the previous phase I trial who had been treated at the recommended phase II dose, were eligible for analysis. The most common drug-related grade 3 to 4 adverse events during the concurrent phase were hematologic and 5.1% of patients experienced grade 3 esophagitis. The response rate was 45.9% (17 of 37 patients), with no complete responses. The 1-, 2-, and 3-year OS survival rates were 79.5%, 56.4%, and 46.2%, respectively. The median OS, time to progressive disease, and progression-free survival was 30.3, 13.7, and 11.8 months, respectively. ConclusionFull-dose cisplatin and pemetrexed can be administered concurrently with conventional doses of thoracic radiation. The median and 1-year OS rates were favorable compared with published clinical trials in this setting. The regimen was tolerable, and the toxicity profile was consistent with the known toxicity profiles of pemetrexed, cisplatin, and radiation.

Imaging of hypoxia with 18F‐FAZA PET in patients with locally advanced non‐small cell lung cancer treated with definitive chemoradiotherapy

For many cancers, tumour hypoxia is an adverse prognostic factor, and increases chemoradiation resistance; its importance in non-small cell lung cancer (NSCLC) is unproven. This study evaluated tumoural hypoxia using fluoroazomycin arabinoside ((18) F-FAZA) positron emission tomography (PET) scans among patients with locoregionally advanced NSCLC treated with definitive chemoradiation. Patients with stage IIIA-IIIB NSCLC underwent (18) F-FAZA PET scans and (18) F-2-deoxyglucose (FDG)-PET scans within 4 weeks of commencing and 8 weeks following conventionally-fractionated concurrent platinum-based chemoradiation (60 Gy). Intra-lesional hypoxic volumes of the primary and nodal masses were compared with FDG-PET metabolic volumes. Baseline tumoural hypoxia was correlated with disease free survival (DFS). Seventeen patients underwent pre-treatment (18) F-FAZA PET and FDG-PET scans. Intra-lesional hypoxia was identified on 11 scans (65%). Baseline lesional hypoxic volumes were consistently smaller than FDG-PET volumes (P = 0.012). There was no statistical difference between the mean FDG-PET volumes in patients with or without baseline hypoxia (P = 0.38). Eight patients with baseline hypoxia had post treatment (18) F-FAZA scans and 6 of these (75%) had resolution of imageable hypoxia following chemoradiation. The DFS was not significantly different between the hypoxic or non-hypoxic groups (median 0.8 years and 1.3 years respectively, P = 0.42). Intra-lesional hypoxia, as detected by (18) F-FAZA PET, was present in 65% of patients with locally-advanced NSCLC and resolved in the majority of patients following chemoradiation. Larger studies are required to evaluate the prognostic significance of the presence and resolution of hypoxia assessed by PET in NSCLC.

A phase II trial of high dose carboplatin and paclitaxel with G-CSF and peripheral blood stem cell support followed by surgery and/or chest radiation in patients with stage III non-small cell lung cancer: CALGB 9531

Purpose We designed a phase II trial to evaluate the efficacy and tolerability of high dose induction chemotherapy with carboplatin and paclitaxel with G-CSF and stem cell support followed by surgical resection and/or chest radiotherapy in patients with stage III non-small cell lung cancer (NSCLC). Patients and methods Patients had pathologically confirmed stage IIIA–IIIB NSCLC, adequate end-organ function, no prior chemotherapy or radiation, and performance status 0–1. Peripheral stem cells were mobilized with G-CSF stimulation on days 1–5 and collected prior to chemotherapy. Chemotherapy consisted of 2 cycles of paclitaxel 250 mg/m 2 over 3 h and carboplatin at an AUC 18 on days 11 and 32, each followed by stem cell reinfusion. Stable and responding patients went on to surgical resection (in patients deemed resectable) followed by post-operative radiation, or to conventional chest radiotherapy to 66 Gy in unresectable patients. Results Twelve patients (11 eligible) were accrued from 1996 to 1999. The 11 patients were predominately male (64%), white (82%), of performance status 0 (64%), and with weight loss less than 5% (55%). The median age was 51 (range 31–63). Ten (10) patients (91%) experienced grade 4 toxicity. There were no lethal toxicities. Grade 3–4 toxicities most commonly reported included: platelets (100%), lymphocytopenia (91%), leukopenia (91%), neutropenia (73%), anemia (55%), pain (45%), and nausea (27%). Three patients (27%) had a partial response to induction chemotherapy. Of the 11 patients, 7 underwent surgical exploration, and 10 received radiation. Two patients were completely resected, 3 patients had incomplete resections, and 2 patients had no resection. There were 4 complete responses and 3 partial responses following surgery and/or radiation. The median overall survival time was 17.8 months. The median failure-free survival time was 8.3 months. One-year and 2-year overall survival are estimated at 64% and 27%, respectively. Conclusions High dose induction chemotherapy with carboplatin and paclitaxel and stem cell support in patients with stage IIIA–IIIB NSCLC produced response rates and survival similar to standard therapy. Excessive toxicity (and cost) suggests that this approach does not merit further investigation.

Unresectable Locally Advanced Non-small Cell Lung Cancer: Early Clinical Experience for Large Volume Targets using Volumetric Modulated Arc Therapy

In recent works dose escalation in radiotherapy (RT) seems to produce an improvement of loco-regional control and overall survival of patients with unresectable locally advanced non small cell lung cancer (NSCLC), where these patients usually present very poor survival and frequent loco-regional failures. In this study the first results deriving from our clinical experience in radiation treatment of stage III NSCLC with volumetric modulated arcs using RapidArc (RA) technology are reported. Making use of two partial arcs with 6MV photon beam, twenty-four consecutive stage IIIA-IIIB NSCLC patients with large volumes of tumor were treated (May 2009-September 2009); 8 of these received sequential and 11 concurrent chemotherapy. All the disease sites identified on the simulation CT and via previous diagnostic images were considered as gross tumor volume (GTV). Sixty-six Gy in 33 fractions to mean planning target volume (PTV) was prescribed where PTV was obtained applying an isotropic margin of 8 mm from the primary tumor and of 5 mm from the involved regional lymph nodes. Some primary and secondary objectives were established in order to preserve organs at risk (OAR): for spinal cord, dose received from 1% of volume had to be lower than 46Gy (D1%<46Gy); for contra-lateral lung, the volume receiving more than 20Gy should be lower than 30% (V20Gy<30%) with a mean dose < 15Gy; for esophagus, D1%<70 Gy. Secondary objectives were: for ipsi-lateral lung, V20Gy as low as possible; for esophagus, V55Gy<30%; for heart, V50Gy<20%, V45Gy<30%. In 56% of patients, after three months from the end of treatment, a partial remission >50% was observed. 81% of patients presented a grade 1 esophageal toxicity while 9% presented a grade 2 acute toxicity; concerning lungs the fraction of patients producing toxicities were found to be 18% and 9%, respectively, for grades 1 and 2. No grade 3 acute toxicity was observed. Performing a dosimetric analysis for GTV, the D1% = 105.6 ± 1.7%, D99% = 96.7 ± 1.8%, D5%-D95% = 6.3 ± 1.4%; for contra-lateral lung the mean dose observed was 13.7 ± 3.9Gy; for heart V45Gy = 9.0 ± 7.0Gy; for spinal cord and esophagus the doses received from 1% of the volume were 39.5 ± 4.0Gy and 67.4 ± 2.2Gy respectively. These dosimetric results support clinical experience despite the large target volumes considered (GTV:299 ± 175cm3, PTV:818 ± 206cm3). Delivery time was 133 ± 7s. The short follow-up does not allow assessment of local control and progression free survival. RapidArc has been proved to be a safe and advantageous treatment modality for NSCLC with large volumes. Long term observation of patients is needed to assess outcome and late toxicity.

A fractionated schedule of oral vinorelbine (NVBo) with cisplatin (CDDP) concomitantly with radiotherapy (RT) after induction chemotherapy (CT) in locally advanced (LA) non-small cell lung cancer (NSCLC): Safety and efficacy results of a phase II trial

7539 Background: NVB+CDDP as induction and concomitant regimen with RT is a recognized treatment in LA NSCLC (Vokes, J Clin Oncol. 2002). The oral formulation of NVB may simplify the administration and a new fractionated schedule may further improve the results during CT-RT. Methods: Non operable stage IIIA-IIIB NSCLC patients (pts) received an induction CT of 2 cycles of NVBiv 25 mg/m2 + CDDP 80 mg/m2 on D1 and NVBo 60mg/m2 on D8 every 3 weeks. Non progressive pts received 2 additional cycles of fixed dose NVBo of 20 mg on D1, D3 and D5, + CDDP 80 mg/m2 on D1 every 3 weeks, combined with a conformal RT at 66 Gy. Results: Between October 05 and May 08, 70 pts were enrolled (68 evaluable for the safety, 64 for response) : 28% stage IIIA, 72% IIIB; 44 % squamous, 30 % adenocarcinoma; 85% male; median age 61 years (range 41;73); median KPS 90%. After induction CT, OR was 42% (PR), Disease Control (DC) = 87%. 4 pts were down-staged and underwent surgery. After CT-RT completion, OR was 55% (CR = 7%), DC = 88%. Main Toxicities (G3–4, % of pts) were: neutropenia (19%), N/V (1%), radic pneumopathy (1%), anorexia (7%). Oesophagitis was recorded in 42% of pts with no G3–4 : G1 (26%), G2 (16%). Conclusions: This new schedule provides a disease control in 88% of pts with 55% OR. Given the optimal tolerance profile of this fractionated administration of NVBo+CDDP, 72% of pts could complete the planned treatment. Furthermore, NVBo taken at home at D3 and D5 reduces the organizational constraints linked to CT-RT. This new scheme offers a well tolerated and efficient therapeutic option in the treatment of non operable IIIA-IIIB NSCLC. Further follow-up is required in order to assess time to progression and survival. [Table: see text]

Effect of preoperative chemoradiation in addition to preoperative chemotherapy: a randomised trial in stage III non-small-cell lung cancer

Preoperative chemotherapy improves survival in patients with stage III non-small-cell lung cancer (NSCLC) amenable to resection. We aimed to assess the additional effect of preoperative chemoradiation on tumour resection, pathological response, and survival in these patients. Between Oct 1, 1995, and July 1, 2003, patients with stage IIIA-IIIB NSCLC and invasive mediastinal assessment from 26 participating institutions of the German Lung Cancer Cooperative Group (GLCCG) were randomly assigned to one of two treatment groups. The intervention group were scheduled to receive three cycles of cisplatin and etoposide, followed by twice-daily radiation with concurrent carboplatin and vindesine, and then surgical resection (those with positive resection margins or unresectable disease were offered further twice-daily radiotherapy). The control group were scheduled to receive three cycles of cisplatin and etoposide, followed by surgery, and then further radiotherapy. The primary endpoint was median progression-free survival (PFS) in patients eligible for treatment after randomisation. Secondary endpoints in patients eligible for treatment after randomisation were overall survival (OS) and the proportion of patients undergoing surgery. Secondary endpoints in patients with tumour resection were the proportion with negative resection margins, the proportion with complete resection, the proportion with histopathological response, and the proportion with mediastinal downstaging. Additionally, exploratory (not prespecified) post-hoc analyses in terms of PFS and OS were done on patients not amenable to resection and on further subgroups of patients undergoing resection. Analyses were by intention to treat. This trial is registered on the ClinicalTrials.gov website, number NCT 00176137. 558 patients were randomly assigned. 34 patients did not meet inclusion criteria and were excluded. Of 524 eligible patients, 142 of 264 (54%) in the interventional group and 154 of 260 (59%) in the control group underwent surgery; 98 of 264 (37%) and 84 of 260 (32%) underwent complete resection. In patients with complete resection, the proportion of those with mediastinal downstaging (45 of 98 [46%] and 24 of 84 [29%], p=0.02) and pathological response (59 of 98 [60%] and 17 of 84 [20%], p<0.0001) favoured the interventional group. However, there was no difference in PFS (primary endpoint) between treatment groups-either in eligible patients (median PFS 9.5 months, range 1.0-117.0 [95% CI 8.3-11.2] vs 10.0 months, range 1.0-111.0 [8.9-11.5], 5-year PFS 16% [11-21] vs 14% [10-19], hazard ratio (HR) 0.99 [0.81-1.19], p=0.87), in those undergoing tumour resection, or in patients with complete resection. In both groups, 35% of patients undergoing surgery received a pneumonectomy (50/142 vs 54/154). In patients receiving a pneumonectomy, treatment-related mortality increased in the interventional group compared with the control group (7/50 [14%] vs 3/54 [6%]). In patients with stage III NSCLC amenable to surgery, preoperative chemoradiation in addition to chemotherapy increases pathological response and mediastinal downstaging, but does not improve survival. After induction with chemoradiation, pneumonectomy should be avoided. German Cancer Aid (Bonn, Germany).

Clinical trial of concurrent low-dose chemotherapy plus radiation vs sequential chemoradiotherapy for unresectable stage III non-small cell lung cancer

Concurrent chemotherapy plus radiotherapy is a trend in treatment of non-small cell lung cancer (NSCLC), but the treatment program is rather complicated and the toxicity is more severe than chemotherapy or radiotherapy alone. The aim of this study is to evaluate the early response and toxicity of concurrent chemoradiotherapy. Eighty unresectable stage IIIA-IIIB NSCLC patients pathologically proved were randomly divided into 2 groups. Group A: patients were treated with concurrent chemotherapy of vinorelbine (12.5mg/m², on days 1, 8, 29, 36) and cisplatin (40mg/m², on days 1, 8, 29, 36) (NP regimen) plus conventional radiotherapy. Patients were irradiated at 1.8-2.0Gy/Fx daily, 5 days per week. The total dose was 60Gy/30-33 Fx. After the radiation, 3 cycles of NP regimen were performed, but the dose of vinorelbine was 25mg/m². Group B: patients received sequential chemoradiotherapy. At first radiation was performed as same as group A. Then chemotherapy of NP (NVB 25mg/m², on days 1 and 8, DDP 80mg/m², on day 1) was followed for 4-5 cycles. The overall response rate in concurrent and sequential groups was 80.0% and 57.5% respectively (Chi-Square=4.71, P < 0.05). Incidences of grade III-IV acute radiation esophagitis and leukopenia were 47.5% and 65.0% in group A, and 25.0% and 42.5% in group B respectively (P < 0.05). The acute radiation pneumonitis rate was 32.5% in group A and 20.0% in group B (P > 0.1). Concurrent chemoradiotherapy is well tolerated in most unresectable stage IIIA-IIIB NSCLC patients. Its early response is better than sequential chemoradiotherapy.

Effect of amifostine on toxicities associated with radiochemotherapy in patients with locally advanced non–small-cell lung cancer

Purpose Radiochemotherapy (RCT) is an effective treatment for locally advanced non–small-cell lung cancer (NSCLC), but can be limited by acute and late toxicities (esophagitis, pneumonitis, and myelosuppression). This trial investigated whether pretreatment with amifostine, a radioprotector, could reduce the incidence of radiochemotherapy-induced acute and late toxicities. Methods and materials Between October 1997 and August 1999, 73 patients with previously untreated Stage IIIa–IIIb NSCLC were randomized to treatment with RCT alone ( n = 36) or RCT plus amifostine (300 mg/m 2 daily i.v. infusion, n = 37). RCT consisted of either paclitaxel (60 mg/m 2) or carboplatin (AUC 2) once weekly during a 5- to 6-week course of conventional radiotherapy given as 2 Gy/5 days/week to a total dose of 55 to 60 Gy. Blood cell counts were measured weekly; esophagitis and acute lung toxicity were evaluated during the treatment course. Treatment efficacy was assessed following World Health Organization criteria for response. Late lung toxicity was assessed at 3 and 6 months after RCT and was graded from 0 to 4 according to the Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer criteria. Results A total of 68 patients were evaluable for toxicity analysis (RCT group, n = 32; RCT + amifostine, n = 36). There was no significant difference between treatment arms in patient baseline characteristics. The incidence of Grade ≥3 esophagitis during RCT was significantly lower for patients receiving amifostine than for patients receiving RCT alone (38.9% vs. 84.4%%, p < 0.001). Furthermore, the incidence of Grade ≥3 acute pulmonary toxicity was significantly reduced in patients treated with RCT plus amifostine compared to patients who received RCT alone (19.4% vs. 56.3%, p = 0.002). At 3 months after RCT, patients treated with amifostine had a significantly lower incidence of pneumonitis than patients who received RCT alone ( p = 0.009). Combined response rates (complete plus partial responses) were 82.2% in the RCT group and 88.8% in the RCT plus amifostine group ( p = 0.498). Conclusion Amifostine is effective in reducing the incidence of both acute and late toxicities associated with RCT in patients with locally advanced NSCLC without compromising antitumor efficacy.