Efficacy Of Concurrent Chemoradiation Research Articles

Randomized phase III Trial of MEDI4736 (durvalumab) as concurrent and consolidative therapy or consolidative therapy alone for unresectable stage 3 NSCLC: A trial of the ECOG-ACRIN Cancer Research Group (EA5181).

TPS8584 Background: Platinum-based concurrent chemoradiation(CRT) followed by one year of the human immunoglobulin G1 kappa (IgG1κ) monoclonal antibody, durvalumab, which blocks the interaction of PD-L1 with its receptors PD-1 and CD80, is the standard of care for locally advanced, unresectable non-small cell lung cancer (NSCLC). Early studies have noted the feasibility of concomitant administration of radiotherapy and immune checkpoint inhibition in NSCLC. EA5181 will evaluate the use of concomitant durvalumab with chemo-radiotherapy for locally advanced NSCLC. Methods: EA5181 is a randomized, multi-center, phase III study for patients with unresectable Stage III NSCLC comparing the efficacy of CRT with concomitant durvalumab to CRT, followed by one year of durvalumab. Eligibility criteria include: an ECOG PS of 0-1, adequate pulmonary function (FEV1 and DLCO both > 40%), no history of auto-immune disease and no past chemotherapy or RT for this lung cancer. Stratification factors include age, sex, stage, and planned concurrent chemotherapy type. Eligible patients with be randomized 1:1 to receive 60Gy RT (2Gy fractions) CRT and durvalumab (Arm A) or 60Gy CRT (Arm B). Investigators will be allowed to choose from three different chemotherapy options: cisplatin/etoposide q 28 days, Pemetrexed/cisplatin q 21 days, and weekly paclitaxel/Carboplatin. Arm A will use 750mg fixed of durvalumab (considered equivalent to 10mg/kg) on days 1, 11, and 21 of RT. Assuming no disease progression, patients in both arms will be followed by monthly (q28 days) fixed dose of 1500mg durvalumab for one year which will be given optimally within 14 days of radiation or when (non)hematologic toxicity is < Grade 2. The primary endpoint is overall survival. Secondary endpoints include progression-free survival, incidence of local/distant progression and toxicity. The target sample size is 660 patients, anticipated to recruit over 55 months, with follow up for an additional 42 months. This provides approximately 82% power if the true hazard ratio for overall survival was 0.75 or less, with 2-sided alpha of 0.05, and assuming a median survival of 42.5 months in the control arm. The study was activated on 04/09/20 and has currently accrued 90 patients on 02/03/21. Clinical trial information: NCT04092283.

A single-center analysis of adjuvant sequential versus ‘sandwich’ chemoradiotherapy for patients with stage III endometrial cancer.

e18101 Background: To determine if the sequencing of chemotherapy with external beam radiotherapy (EBRT) in the adjuvant setting for FIGO stage III endometrial cancer impacts 2-year progression free survival (PFS). Methods: As part of our Gynecologic Oncology Multidisciplinary Group's initiative to establish an institutional guideline for the adjuvant treatment of Stage III endometrial cancer, we reviewed 144 cases identified by our cancer registry and departmental database. Treatment regimens were divided into three categories: sequential therapy with six cycles of carboplatin/taxane followed by EBRT, concurrent cisplatin for two cycles with EBRT followed by four cycles of carboplatin/taxane, or ‘sandwich’ therapy with three cycles of carboplatin/taxane followed by EBRT followed by three cycles of carboplatin/taxane. The published results of the phase III GOG-258 study called into question the efficacy of concurrent chemoradiation. Therefore, we only compared sequential versus ‘sandwich’ therapy using a Chi-Square analysis. We conducted a retrospective chart review to assess if patients were able to complete the prescribed six cycles and EBRT, and then measured their PFS at two years. We hypothesized that there would be no difference in PFS between the two groups. Results: There were no significant differences in clinical or pathologic factors between patients treated with either regimen. Ninety-four patients (65%) had stage IIIC disease. The majority of patients received six cycles of paclitaxel with carboplatin. Median EBRT dose was 45 Gy. There was no statistically significant difference in the estimated 2-year PFS between the sequential and ‘sandwich’ groups, which were 82% and 82.5%, respectively (p = 0.84). Conclusions: Adjuvant chemoradiation for FIGO stage III endometrial cancer given sequentially or in a ‘sandwich’ fashion appears to offer equally excellent early clinical patient outcomes.

Efficacy of Concurrent Chemoradiation in Locally Advanced Squamous Cell Carcinoma of Head and Neck

Efficacy of Concurrent Chemoradiation in Locally Advanced Squamous Cell Carcinoma of Head and Neck

Concurrent chemoradiation with paclitaxel in locally advanced head and neck cancer: A feasibility study from tertiary cancer care center

Background: In India, the majority of the head and neck squamous cell carcinoma (SCC) of head and neck (60–80%) presented in locally or locoregionally advanced stage but non-metastatic disease as compared to 40% in developed nations. Uncontrolled local and/or locoregional disease causes most fatalities and predominant failure pattern is local and/or locoregional. Concurrent chemoradiation (CRT) is now standard of care. However, regarding either the optimal scheduling of chemotherapy regimen or radiotherapy (RT) dose fractionation scheme, no consensus exists. Paclitaxel is also active agents against squamous cell carcinoma of head and neck. Weekly paclitaxel appeared to be equivalent to weekly cisplatin with concurrent radiation in the treatment of locally advanced SCC of head and neck cancer (HNC). Concurrent chemoradiotherapy with paclitaxel in locally advanced head and neck malignancy is recommended in NCCN Guideline. Objectives: The aim of our study is feasibility and efficacy of CRT with paclitaxel for the treatment locally advanced HNC in our institute, Nil Ratan Sircar Medical College and Hospital, Kolkata. Material and Methods: Between January 2014 and December 2018 ninety eight (98) previously untreated patients with locally advanced histologically confirmed carcinoma oral cavity, oropharynx, and hypopharynx treated with CRT. Chemotherapy consisted of paclitaxel at a dose 40 mg/m2 over 1 h given once weekly from 1st week of RT, up to 4–6 cycles. RT consisted of 66 Gy/33#/61/2 weeks, 2 Gy/fraction, delivered by two parallel opposed lateral face and neck and low anterior neck portal, in cobalt 60 machines. Toxicity was graded using Common Terminology Criteria for Adverse Events v3. To assess response to therapy contrast-enhanced computed tomography (CECT) head and neck and/or magnetic resonance imaging head and neck; CECT chest or whole-body fluorodeoxyglucose and positron emission tomography computed tomography scan were done. Results: Overall complete response (CR) rate seen in 68% and partial response seen in 32% patients. Two-year disease-free survival, progression free survival, and overall survival were 59%, 72% and 85%, respectively. Grade II acute skin reaction seen in 45% patients and Grade III acute skin reaction seen in 55% patients. Similarly, Grades II and III mucosal reaction is seen in 48% and 52% patients. All patients experience Grade II dysphagia and managed conservatively. Conclusions: CRT with paclitaxel in locally advanced HNC is safe and confers high CR rate with acceptable toxicity. However, more randomized study with large number of patients is needed to come to conclusions regarding its efficacy.

Neoadjuvant concurrent chemoradiation in male breast cancer: Experience from a tertiary cancer center.

Male breast cancers (MBC) account for 1% of all breast cancers. Neoadjuvant concurrent chemoradiation (CTRT) is not the standard of care for treating breast cancer. However, in our center, it has been routinely used in patients with locally advanced breast cancer to downsize the tumor and make it amenable to surgery. This study was conducted to examine the clinical and pathological profile and outcomes of patients with MBC treated at our institute with neoadjuvant CTRT. The study was conducted at a tertiary cancer center and was retrospective in nature. All MBC patients treated with neoadjuvant CTRT at our center between 2001 and 2016 were enrolled in the study. Data were retrospectively extracted from the patients' case records. Kaplan-Meier method was used for survival analysis and the outcome variables were compared using the log-rank test. Thirty-one MBC patients who received neoadjuvant CTRT were analyzed in this study. The median age of the patients was 53 years. Stage IIB disease was observed in 8/31 (26%) patients, stage III in 20/31 (64%), and stage IV in 3/31 (10%) patients. There was no grade 3 or 4 toxicity due to CTRT. Surgery was performed in 29/31 (94%) patients and none of the patients had a pathological complete response. The median duration of follow-up was 95.3 months. The 8-year event-free survival and overall survival for stage IIB, III, and IV were 75%, 50%, and 0% and 87.5%, 69%, and 0%, respectively. This is the first study to report on the use of neoadjuvant CTRT in MBC. Prospective evidence from phase-3 randomized controlled trials on the safety and efficacy of CTRT in breast cancer is required before its routine use can be recommended.

Favorable outcomes with chemoradiation and surgery for locally advanced non-small cell lung cancer: The BC Cancer Agency Vancouver experience.

7020 Background: The role of surgery following concurrent platinum-based chemotherapy and radiation for locally advanced non-small cell lung cancer (NSCLC) remains controversial, with high surgical mortality rates reported in a large randomized clinical trial. In this retrospective study, we evaluated the safety and efficacy of concurrent chemoradiation with or without surgery over an 11 period at the BC Cancer Agency. Methods: Patients were identified by the Vancouver Centre Pharmacy database. Charts were reviewed and data extracted included patient characteristics, weight loss, performance status, and method of mediastinal staging. Outcome measures were overall survival, pathological response rate, and treatment-associated morbidity and mortality. Results: Between January 1999-2010, 177 patients were identified with locally advanced NSCLC (stage IIIA/B) treated with platinum and etoposide and ≥40Gy radiation therapy, with or without surgical resection. The majority of treatment plans were reached by a multidisciplinary conference consensus. 74% (n=131) of patients received chemoradiation alone (bimodality therapy) and 36% (n=46) received chemoradiation followed by surgical resection (trimodality therapy). Among the trimodality therapy group, 16 patients underwent pneumonectomy and 30 lobectomy. Conclusions: In this series, bimodality therapy for patients with locally advanced NSCLC had similar treatment associated mortality and survival outcomes as reported in the literature. Trimodality therapy was associated with low treatment mortality rates and favourable survival. These two groups cannot be directly compared in this retrospective study. However, these results support a multidisciplinary approach to identify and carefully select patients with locally advanced NSCLC to undergo additional surgical resection following concurrent chemoradiation. [Table: see text]

Concurrent chemoradiation-related superior mesenteric artery occlusion in the patient with advanced endometrioid endometrial cancer after surgery

The incidence of endometrial cancer (EC) has increased and it has approximately 16% of gynecologic cancers in Korea. For locoregional or distant recurrence, adjuvant treatment after surgery is very important in patients with intermediateor high-risk EC (IHR-EC). Recently clinical trials for treating patients with IHR-EC are focused on the effi cacy of concurrent chemoradiation (CCR). However, increase in intestinal complications in the group of radiotherapy combined with chemotherapy was reported. In case of chemoradiation-related superior mesenteric artery (SMA) occlusion, it could be fatal nevertheless with intensive care. We present a case report of radiation-related arteritis leading to stenosis in SMA, which led the patient with EC to death in a year after CCR.

Phase II Study of Concurrent Chemoradiation in Combination With Erlotinib for Locally Advanced Esophageal Carcinoma

To investigate the feasibility and efficacy of concurrent chemoradiation in combination with erlotinib for locally advanced esophageal carcinoma. Twenty-four patients with locally advanced esophageal carcinoma were treated with concurrent chemoradiotherapy. A daily fraction of 2.0 Gy was prescribed to a total dose of 60 Gy over 6 weeks. Concurrent paclitaxel (135 mg/m(2), d(1)) and cisplatin (20 mg/m(2), d(1-3)) were administered on Day 1 and Day 29 of the radiotherapy. Erlotinib, an oral epidermal growth factor receptor-tyrosine kinase inhibitor, was taken by every patient at the dose of 150 mg daily during the chemoradiotherapy. The median follow-up of the 24 patients was 18.6 months (range, 7.1-29.6 months). The 2-year overall survival, local-regional control, and relapse-free survival were 70.1% (95% CI, 50.4-90%), 87.5% (95% CI, 73.5-100%), and 57.4% (95% CI, 36.3-78.7%), respectively. During the chemoradiotherapy, the incidences of acute toxicities of Grade 3 or greater, such as leucopenia and thrombocytopenia, were 16.7 % (4/24) and 8.3% (2/24). Application of concurrent chemoradiotherapy in combination with erlotinib for locally advanced esophageal carcinoma yielded satisfactory 2-year overall survival and local-regional control. The toxicities were well tolerated.

Comparison of tolerability and efficacy of concurrent chemoradiation (CRT) for anal squamous cell carcinoma (SCC) in HIV-positive (HIV+) and -negative (HIV-) patients (pts)

4606 Background: It is believed that the prognosis of anal SCC is poor in HIV+ pts, and their appropriate treatment is uncertain. We compared the tolerability and efficacy of concurrent CRT as definitive therapy for anal SCC in HIV+ and HIV-/unknown pts in the HAART- era. Methods: Pts serially diagnosed and treated in a single institution from Apr/2000 to May/2007. Definitive CRT consisted of 45- 59.4Gy, divided in 5 fractions/week, given with concurrent mitomycin-C (MMC) 15mg/m2D1 IV and 5-fluoruracil (5FU) 1g/m2/d IV, continuous infusion, D1-D4 and D29-D32. Baseline hematologic, hepatic and renal functions were normal in all pts, and the same treatment was delivered irrespective of HIV-status. HIV+ pts were under antiretroviral therapy according to standard recommendations. Results: 78 pts were included in the analysis, median age 56.5y (23–85y), 63 female (81%). Stage: Tis (3 pts), I (4), II (26), IIIA (15), IIIB (20), IV (1). Nine pts were identified as HIV+. HIV+ pts were younger (39.4 vs. 59.2 y, p<0.0001) and predominantly male (8/9 pts). No difference in tumor stage or grade was detected in HIV+ pts. For all pts, the median dose of RT was 45Gy, given over 42d. No difference in terms of treatment duration or administered CRT intensity between HIV+ or HIV- /unknown pts was observed and treatment was well tolerated. Complete response (CR) was achieved in 45 pts (58%), partial response in 7 pts (9%), stable disease in 6 pts (8%) and disease progression in 3 pts (4%). No difference was seen in HIV+ pts in terms of CR rate (6/9 CR (67%), p=0.664). With a mean follow-up of 25mo, 14 deaths have occurred. The median overall survival (OS) was not reached (NR). The 2-y OS rate was 78%. No difference in OS was seen between HIV+ or HIV-/unknown pts (NR in both groups, p=0.248), and a 2-y OS rate of 100% was observed in HIV+ pts. We also observed both longer median PFS (NR vs. 11.5 mo, p=0.0009, HR 0.254, 95%CI 0.034–0.417) and median OS (NR vs. 12.9 mo, p=0.0007, HR 0.180, 95%CI 0.013–0.309) among patients that needed no colostomy. Conclusions: In this group of anal SCC pts no differences in terms of prognosis, treatment tolerance or efficacy could be identified based on HIV status, and the standard 5FU/MMC-based CRT could be delivered successfully. No significant financial relationships to disclose.

Long-term results of concurrent and adjuvant chemotherapy for advanced nasopharyngeal carcinoma

6056 Background: Preliminary results of a factorial trial investigating concurrent chemoradiation (CRT) and adjuvant chemotherapy (AC) for nasopharygngeal carcinoma (NPC) was reported in 2004 (JCO 22 (13): 2643–2653). This is a report on the long-term follow-up results of the study. Methods: Ho's stage T3 or N2 /N3 or > 4cm neck node, M0 disease were eligible. Patients were first randomized to receive CRT or RT alone and then further randomized to receive AC or no AC after completion of CRT/RT. Patients randomized to CRT received UFT (uracil and tegafur in 4:1 molar ratio) 200mg, 3 times a day, during radiotherapy. AC consisted of alternating PF (cisplatin 100mg/m2 D1 and 5FU 1g/m2 D1–3) and VBM (vincristine 2mg, bleomycin 30mg and methotrexate 150mg/m2, all on D1) for 6 cycles. The 4 treatment arms were: A. RT, B. CRT, C. RT + AC, D. CRT + AC. Patients in arms A and C were compared with those in arms B and D (i.e. RT vs. CRT) for efficacy of CRT. Patients in arms A and B were compared with those in arms C and D (i.e. no AC vs. AC) for efficacy of AC. Loco- regional control (LRC), distant metastases free survival (DMFS), failure-free survival (FFS) and disease-specific survival (DSS) were estimated with Kaplan-Meier methods and compared with log-rank test. Results: From May 1995 to October 2001, 222 patients were recruited. 3 patients were excluded from analysis. Median follow up time was 7 years. There were 55, 53, 54, 57 patients in arm A, B, C, D respectively. The 7-year LRC of the 4 arms were 64.2%, 74.8%, 78.7%, 78.8% respectively; DMFS were 71.7%, 85.8%, 65.5%, 80.4%; FFS were 51.7%, 69%, 53.2%, 64.4%; DSS were 71.7%, 75.4%, 66.1%, 81.5%. CRT significantly improved the DMFS and FFS compared with RT (p=0.014 and 0.016 respectively). There was a trend of improvement in DSS with CRT also (p=0.057). The use of AC failed to improve survival. Multivariate analysis showed CRT, T stage and N stage were significant for both FFS and DSS. Conclusions: CRT significantly improved DMFS and FFS in advanced NPC. The benefit of CRT was confirmed on long-term follow-up. No significant financial relationships to disclose.

External beam radiotherapy and high-dose brachytherapy combined with cisplatin and paclitaxel in patients with advanced cervical carcinoma

Objective. The aim of the present study was to evaluate toxicity and efficacy of concurrent chemoradiation with cisplatin and paclitaxel and high-dose rate (HDR) brachytherapy in patients with locally advanced cervical cancer. Patients and methods. 19 patients with locally advanced cervical carcinoma were treated with external beam radiotherapy (EBRT) to the pelvis ± paraaortic nodes, HDR brachytherapy, cisplatin at doses of 50 mg/m 2 in weeks 1 and 4, and weekly paclitaxel at 50 mg/m 2 in weeks 1–5 during years 2000–2002. Chemotherapy was administered until leukopenia ≤2500/mm 3, thrombocytopenia <100,000/mm 3, and/or hemoglobin level <100 g/l occurred. The median follow up was 36 months (range 25–47). Results. Only four patients were able to tolerate the complete intended course of radiochemotherapy. Chemotherapy was stopped in two patients because of allergic reaction and in one patient because of deep thrombosis. In 12 other cases, chemotherapy was discontinued for hematological toxicity. The 3-year disease free survival was 66%, the 3-year overall survival was 74%. Conclusion. The hematological toxicity was the main factor limiting administration of cisplatin at 50 mg/m 2 in weeks 1 and 4 and weekly paclitaxel at 50 mg/m 2 in weeks 1–5 concomitantly with extended field radiotherapy of locally advanced cervical carcinoma.