Concurrent Chemoradiation Regimens Research Articles

Trial in Progress: Adaptive RADiation Therapy with Concurrent Sacituzumab Govitecan (SG) for Bladder Preservation in Patients with MIBC (RAD-SG).

A substantial proportion of patients with muscle invasive bladder cancer do not receive curative intent therapy, especially if unfit for or refuse radical cystectomy. Concurrent chemoradiation is an effective alternative to radical cystectomy, however systemic radio-sensitizing chemotherapy may have off target side effects. A Phase I study is accruing which will investigate the concurrent administration of a bladder cancer targeted antibody drug conjugate (Sacituzumab Govitecan) with radiotherapy. This trial in progress is a Phase I study of Adaptive RADiation therapy with concurrent Sacituzumab Govitecan (SG) for bladder preservation in patients with muscle invasive bladder cancer (MIBC). Eligible patients will have localized muscle invasive bladder cancer (MIBC) confined to the bladder. The initial cohort is expected to accrue 20 patients. The primary endpoint is to establish the safety, tolerability, and feasibility of bladder preservation therapy treatment with concurrent SG and adaptive image-guided radiation therapy for patients with localized MIBC. The secondary endpoints are to determine the bladder intact event-free survival (BI-EFS) with concurrent SG and radiation therapy for MIBC and compare to historical controls with other concurrent chemoradiation regimens. BI-EFS is defined as the time from treatment to the first documented occurrence of residual/recurrent MIBC, nodal or distant metastases on imaging, radical cystectomy, or death from any cause. Sacituzumab Govitecan targets TROP-2, a surface protein expressed in urothelial cancers of the bladder. SG will be delivered IV, 10 mg/kg, 21-day cycles for 1 loading cycle prior to radiation and two subsequent cycles with concurrent adaptive radiotherapy over a period of 6 weeks (64 Gy). Correlative objectives (Supported by NCI/NIH U54) and will involve 1) elucidation of the genetic and microenvironmental mechanisms that drive efficacy and resistance to combined ADC plus radiation therapy and 2) characterization of tumor clonal dynamics, immune repertoire editing, and imaging changes following treatment with SG plus radiation. To be determined. To be determined.

Comparison of sequential versus concurrent chemoradiation regimens in non-metastatic muscle-invasive bladder cancer.

The treatment approach for non-metastatic bladder cancer is guided by an invasion of the muscular layer of the bladder wall. Radical cystectomy is the recommended treatment for muscle-invasive disease. However, it has considerable morbidity and mortality and is not suited for many patients. Trimodality therapy consisting of chemoradiation after transurethral resection of bladder tumor offers a definitive approach with bladder-sparing potential. However, there is a lack of research defining the optimal combination of chemotherapy and radiation in this setting. We extracted patient data from the National Cancer Database to compare survival outcomes and demographic factors in 2,227 non-metastatic bladder cancer patients who were treated with chemotherapy sequential to or concurrently with radiation. Sequential treatment was defined as chemotherapy beginning >14 days before radiation, and concurrent was defined as beginning within 14 days of the first radiation. The sequential treatment group patients were younger (mean age, 74 vs. 78 years; p < 0.001) with more advanced disease. We found no difference in overall survival between patients who received chemotherapy sequential to radiation and those who received concurrent chemoradiation only (p = 0.533). Our data are concordant with a previous prospective study, and support that chemotherapy prior to radiation does not decrease survival outcomes relative to patients receiving only concurrent chemoradiation. Given that the sequential group had an overall higher stage but no difference in survival, downstaging chemotherapy prior to radiation may be helpful in these patients. Further studies including a larger, multi-institutional clinical trial are indicated to support clinical decision-making.

Efficacy and safety of camrelizumab in combination with radiation and chemotherapy for recurrent or metastatic cervical cancer.

5542 Background: Cisplatin-based concurrent chemoradiation regimens have been suggested to be beneficial in recurrent or metastatic cervical cancer. Immunotherapy has also shown good therapeutic efficacy in recurrent or metastatic cervical cancer. Among them, Pembrolizumab in combination with chemotherapy has been used for first-line treatment of advanced PD-L1-positive cervical cancer. Meanwhile, Camrelizumab has shown good anti-tumor activity and manageable toxicity in patients with locally advanced cervical cancer. The primary objective of this study is to evaluate the efficacy and safety of Camrelizumab in combination with concurrent chemoradiation in patients with recurrent or metastatic cervical cancer. Methods: Patients diagnosed with recurrent or metastatic cervical cancer received Camrelizumab combined with concurrent chemoradiotherapy, radiotherapy:External beam radiotherapy (EBRT) 1.8-2.15 Gy/f, a total of 28 fractions; Brachytherapy: high-risk CTV using image guidance 28 Gy in 4 fractions (18 Gy in 3 fractions for posthysterectomy recurrent patients); chemotherapy regimen used TP regimen (paclitaxel: 175 mg/m2, cisplatin: 75 mg/m2, Q3W 6 cycles); Camrelizumab 200 mg Q3W 6 cycles. The primary endpoint of this trial was objective response rate (ORR), and secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and incidence of adverse reactions. Results: From September 16, 2020 to September 30, 2022, a total of 29 patients were recruited. 27 of these patients completed 6 cycles of planned treatment. 27 patients had a median age of 53 years (33-73 years), ECOG PS 0 (n = 8), ECOG PS 1 (n = 14), ECOG PS 2 (n = 1). The ORR rate was 96.30% (26/27), including 17 patients with CR, 9 patients with PR, and 1 patient with SD Treatment-related AEs were mainly lymphocyte count decreased, anemia, and white blood cell count decreased, with overall safety manageable and no treatment-related deaths. Conclusions: Camrelizumab combined with concurrent chemoradiation in patients with recurrent or metastatic cervical cancer has good efficacy, low side effects and acceptable toxicity. Clinical trial information: NCT04884906 .

Primary Hypothyroidism in Patients Exposed to Therapeutic External Beam Radiation: Non-randomized Comparative Study.

Background Cancer patients are not routinely assessed for thyroid function after external beam radiotherapy (EBRT) to the neck, despite hypothyroidism being a known side effect of EBRT. So, this study aimed to assess the incidence of hypothyroidism after therapeutic external beam radiotherapy to the neck and to determine the time for the development of hypothyroidism. Methodology A non-randomized prospective comparative study was done at a tertiary care center from April 2018 to September 2020. Any cancer patients who were euthyroid before radiotherapy and are planned to receive EBRT to the neck were included as cases, whereas controls were selected from the patients who were euthyroid before radiotherapy and were planned to receive EBRT to the site other than the neck. A total of 100 participants in each case and control group were selected. Data were collected on participants' age, gender, primary tumor site, treatment modality, total radiation dose along with concurrent chemoradiation regimens. Details of blood chemistry including thyroid hormone levels were collected during the pre-radiation phase and post-radiation phase. After the completion of radiotherapy, both the patients and controls were followed up periodically at three months, six months, nine months, 12 months, and finally at 15 months post-radiation. Data were analyzed and interpreted to pursue defined objectives by using tables and graphs using Microsoft Excel and IBM SPSS, version 26.0 (Armonk, NY: IBM Corp.). The chi-square test was applied to find out the association of different variables with the development of hypothyroidism. P-values<0.05 were considered significant throughout. Results According to our findings, the incidence of hypothyroidism following external beam radiotherapy to the neck where radiation portals included a portion or the entire thyroid gland was 16% and 4%, when the radiation given to sites other than neck region.The difference in incidence between the case and control groups was found to be statically significant (p<0.05). However, it was found that age, gender, the primary tumor site, total radiation dose, and treatment modality had no significant effects on hypothyroidism development. The median time duration to become hypothyroid after EBRT was 12 months. Conclusions The monitoring of thyroid function should become a part of routine follow-up procedures in all cancer patients who receive neck radiation as part of their treatment.

GOTIC-018: Phase I, open-label, multicenter study to assess the safety of pre- and co-administration of ONO-4538 (nivolumab) with concurrent chemoradiation (CCRT) in patients (pts) with locally advanced cervical carcinoma (LACvCa).

5529 Background: LACvCa has a poor prognosis. CCRT is the standard treatment for LACvCa, and the 5-year survival rate is estimated at around 60%. Nivolumab (Nivo), an anti-PD1 monoclonal antibody, showed clinical activity in recurrent or persistent CvCa pts. Nivo may enhance antitumor immune responses induced by CCRT. The safety and feasibility of Nivo plus CCRT for LACvCa pts has not yet been reported. We report data from a phase I trial evaluating safety and feasibility of pre- and co-administration of Nivo with CCRT in pts with LACvCa (GOTIC-018; JMA-IIA00425). Methods: The treatment plan in cohort A is co-administration of Nivo (240mg/body once every 2 weeks) with CCRT followed by maintenance therapy with Nivo. The treatment plan in cohort B is pre- (two doses of Nivo before CCRT) and then co-administration of Nivo with CCRT followed by Nivo maintenance. The CCRT regimen includes 4 or more cycles of cisplatin (40 mg/m2 weekly) and external beam radiotherapy (EBRT) followed by brachytherapy. The Nivo maintenance therapy was scheduled for 52 weeks after completion of CCRT. The primary objective is the rate of Grade≧3 adverse events (AEs) during the acute phase, which is defined as 90 days from the start date of EBRT. Secondary objectives include the incidence of dose limiting toxicity (DLT) and progression-free survival. Results: A total of 30 patients, 15 patients in each cohort, was enrolled in this study. This report is a safety evaluation in the acute phase of the study. There were 1 stage IVA, 11 stage IIIB, 16 stage II and 2 stage IB tumors based on FIGO 2009. 28 squamous cell and 2 adeno/adenosquamous carcinomas were included. No DLT was observed in the first 6 DLT-evaluable pts in each cohort. All 30 patients completed planned EBRT and brachytherapy. 2 and 0 patients required a break from EBRT in cohort A and B, respectively. The median cycles of cisplatin administration was 5 and 6 in cohort A and B, respectively. 2 and 0 patient required cisplatin dose reduction in cohort A and B, respectively. 1 patient required cisplatin discontinuation in each cohort. The median cycles of Nivo administration were 6 and 9 in cohort A and B, respectively. 1 patient required Nivo discontinuation due to AEs in each cohort. All patients experienced Grade≧3 AEs. Most common Grade≧3 AEs were neutropenia (60.0 and 26.7% in cohort A and B, respectively), anemia (13.3 and 16.7%) and diarrhea (13.3 and 26.7%). In cohort B, no patients required delay in starting CCRT due to the AEs related to pre-administration of Nivo, and no patients had disease progression before starting CCRT. Conclusions: No DLT was reported during the acute phase in both cohort A and B, and no new safety signals were observed. Addition of pre-and co- administration of Nivo appears safe and feasible in patients with LACvCa treated with CCRT. Clinical trial information: JMA-IIA00425.

CLINICAL OUTCOME USING WEEKLY PACLITAXEL WITH RADIATION IN LOCALLY ADVANCED LUNG CANCER

Background: Non-small cell lung cancer is the second most common malignancy worldwide with very high mortality rate. The aim of this study is to evaluate the locoregional response and toxicity prole using weekly paclitaxel along with radiation in locally advanced inoperable non-small cell lung cancer in a tertiary care centre. A prospective analysis was Methods: carried out on non-metastatic locoregionally advanced non-small cell lung cancer patients who were treated in the Radiotherapy Department, Medical College, Kolkata from January 2014 to July 2015. The patients received concurrent chemoradiotherapy with weekly paclitaxel. Out of 54 patients Results: analysed, overall response rate was 81.48% and complete response rate was 12.96%. The progression free survival rate at 1 year was 41.30%. Median progression free survival was 10.00 ±0.40 months. The most common toxicities were acute pharyngeal and esophageal toxicity. The toxicity was acceptable and response was Conclusion: comparable with other platinum based concurrent chemoradiation regimens.

Matched pair analysis for comparison of survival outcome of alternative regimens to standard three-weekly cisplatin-based concurrent chemoradiation of head and neck cancer.

BackgroundTo compare head and neck cancer (HNC) patients treated with three-weekly versus weekly cisplatin-based or other chemotherapy-based concurrent chemoradiation (CRT) and CRT with versus without induction chemotherapy (ICT) to investigate differences in overall survival (OS) and cancer-specific survival (CSS).MethodsHNC patients treated with definitive or adjuvant CRT at Roswell Park Comprehensive Cancer Center between 2003 and 2017 were retrospectively reviewed. Propensity score matching was performed to obtain three sets of balanced matched pairs: three-weekly and weekly cisplatin CRT, three weekly and non-cisplatin CRT, CRT with and without ICT. Multivariate Cox regression and Kaplan-Meier analyses were used to estimate and compare survival outcomes.ResultsA total of 623 patients received either definitive (81%) or post-operative (19%) RT. Of these, 283 patients concurrently received three-weekly cisplatin (45%); 189 patients (30%) received weekly cisplatin; 151 patients (24%) received non-cisplatin regimen. Median follow-up was 55.4 months (interquartile range, 38.0–88.7). Patients who received CRT alone and those who received ICT and CRT had no difference in 5-year OS (51.5% and 41.0% respectively, P=0.53) and CSS (64.9% and 49.7% respectively, P=0.21). Compared to patients who received three-weekly cisplatin, patients who received weekly cisplatin had no difference in 5-year OS (59.3% vs. 54.1%, P=0.35) and CSS (70.3% vs. 62.4%, P=0.09); patients who received non-cisplatin CRT also had no difference in 5-year OS (54.5% vs. 58.3%, P=0.51) and CSS (67.5% vs. 64.7%, P=0.45).ConclusionsNo significant difference in OS and CSS was observed in any of the three pairs of CRT regimens. ICT prior to CRT did not improve survival of CRT alone. Non-cisplatin and weekly cisplatin regimens did not prove to be inferior to the standard three-weekly cisplatin.

S-1 plus cisplatin with concurrent radiotherapy for stage III non-small cell lung cancer: A meta-analysis (PRISMA) of randomized control trials.

Introduction:The present study aims to assess the efficacy and safety of S-1 plus cisplatin as concurrent chemoradiation (experimental group [EG]) compared with standard concurrent chemoradiation regimens (control group[CG]) in patients with local advanced non-small cell lung cancer.Methods:The Cochrane library, pubmed, and Ovid (elsevier) were retrieved. The included randomized controlled trials (RCT) were evaluated, and the statistical analysis was performed using RevMan 5.3 software. Cochrane handbook was applied to evaluate the methodological quality. Statistical significance was considered as P <.05.Results:There were 5 randomized control trials identified eligible for the meta-analysis. Meta-analysis of the pooled date suggested that overall survival (OS) (HR, 0.81; 95% CI, 0.58–1.13; P = .21, heterogeneity P = 1.00, I2 = 0%), progressives free survival (PFS) (HR, 0.82; 95% CI, 0.62–1.09; P = .18, heterogeneity P = .83, I2 = 0%) and 1,2,3-year OS (1-year OS: RR 1.03; 95% CI: 0.92–1.15, p = 0.59), (2-year OS: RR 1.14; 95% CI: 0.98–1.34, P = .09), (3 -year OS: RR 1.14; 95% CI: 0.90–1.44, P = .29) were not significantly different. The combination of S-1 and cisplatin had lower grade 3 or 4 leukocytopenia, neutropenia, (RR = 0.54, 95% CI: 0.38–0.75, P = .0003; RR = 0.23,95% CI: 0.14–0.36, P <.00001;, respectively). The rates of nausea, diarrhea, thrombocytopenia, pneumonitis, anorexia, anemia, febrile neutropenia were much the same in the 2 groups (RR = 1.35, 95% CI: 0.68–2.68, P = .38; RR = 1.85, 95% CI: 0.61–5.60, P = .28; RR = 1.67, 95% CI: 0.88–3.17, P = .12; RR = 1.19, 95% CI: 0.44–3.21, P = .73; RR = 1.35, 95% CI: 0.68–2.68, P = .38; RR = 0.86, 95% CI:0.55–1.34, P = .50; RR = 0.63, 95% CI:0.35–1.14, P = .13;, respectively).Conclusions:This meta-analysis of 5 randomized control trails demonstrates that EG results similar OS, PFS, and 1,2,3-year OS, compared with CG, with lower risk of leukocytopenia, neutropenia.

Sandwich/Sequential but not Concurrent Chemoradiation Therapy is Associated with Overall Survival for Advanced Endometrial Carcinomas

The GOG 0258 randomized controlled trial demonstrated no benefit in relapse free survival with concurrent chemoradiation (CRT) versus chemotherapy (C) alone for stage III-IVA endometrial carcinomas. We sought to determine whether the delayed initiation of RT with sandwich or sequential CRT regimens is associated with improved overall survival (OS). We utilized the National Cancer Center Database to identify all patients eligible for the GOG 0258 trial (predominantly stage III-IVA carcinomas). All patients underwent surgical staging and received adjuvant multi-agent C with or without RT within 90 days of surgery. Patients who received adjuvant RT were divided into three sequencing regimens: concurrent (RT within 14 days of C), sandwich (RT between 14 and 126 days after C), and sequential (RT between 126 and 180 days after C). A Cox proportional hazards multivariate model was used to determine the associations between each of the sequencing regimens against C alone as a baseline, after adjusting for clinical (histology, age ≥ 65, Charlson co-morbidity index, stage, nodal evaluation, lymphovascular invasion, peritoneal cytology, margin status) and demographic (facility type, race) factors. Subgroup analyses were conducted for the endometrioid and stage IIIC subgroups. We identified 11,644 patients who were diagnosed between 2006 and 2014. The median follow-up was 39.4 months (IQR 23.9, 63.3). The numbers of patients who received C alone, concurrent CRT, sandwich CRT, and sequential CRT were 6911 (59%), 486 (4%), 2634 (23%), and 1613 (14%). 5156 (44%) had grade endometrioid histology, and 7006 (60%) had stage 3C disease. With C alone as a baseline, sandwich (HR = 0.73; p < 0.01) and sequential (0.69; p < 0.01) CRT, but not concurrent CRT (0.87; p = 0.14), were associated with improved OS. Similar results were obtained for the endometrioid subgroup: concurrent (0.91; p = 0.48), sandwich (0.70; p < 0.01), and sequential (0.73; p < 0.01). For the stage IIIC subgroup, the association for concurrent CRT did not reach significance (0.81; p = 0.06), while sandwich (0.70; p < 0.01), and sequential (0.66; p < 0.01) regimens remained significant. These results support the use of sandwich or sequential RT with multi-agent chemotherapy in the adjuvant treatment of women with advanced stage endometrial cancer. Further prospective clinical validation of these results is warranted.

Concurrent Radiotherapy and Triweekly Carboplatin for the Definitive Treatment of Locally Advanced Laryngeal Carcinoma.

In 2003, our institution adopted triweekly carboplatin (tCb) area under the curve (AUC) 5 as an alternative to high-dose cisplatin (100 mg/m) for select patients receiving definitive concurrent chemoradiation for locally advanced laryngeal carcinoma (LALC). Here, we present our experience and outcomes with this definitive concurrent chemoradiation regimen. From January 2003 through December 2013, 53 patients with stage III (60%) or IVA (40%) LALC were treated with tCb AUC 5 and concurrent radiotherapy to 70 Gy without neoadjuvant chemotherapy. Reasons for using carboplatin instead of cisplatin in these patients were: age 70 and older (21%), poor renal function (6%), presence of 1 or more major comorbid condition(s) (36%), and per discretion of the treating medical oncologist (38%). Primary disease site was glottis in 22 (42%) patients and supraglottis in 31 (58%) patients. Median follow-up time was 63 months for surviving patients. Out of the 53 patients, 43 (81%) received all 3 cycles of carboplatin and all patients received their intended dose of radiotherapy. Although 17 (32%) patients required a feeding tube during treatment, only 2 (4%) required it long term. There were no acute treatment-related grade 4 or 5 hematologic toxicities. On last follow-up, 14 (26%) patients had died of intercurrent disease. For the subgroup of "RTOG 9111 eligible" patients in our cohort (n=46), 5-year estimates of overall survival, disease-free survival, laryngectomy-free survival, larynx preservation, and locoregional control were: 49%, 42%, 39%, 80%, and 63%, respectively. In patients with LALC who are suboptimal candidates for high-dose cisplatin, our experience suggests that tCb AUC 5 with concurrent radiotherapy provides acceptable outcomes with tolerable toxicity.

Efficacy and safety of concurrent chemoradiotherapy with cisplatin and docetaxel in patients with locally advanced nasopharyngeal cancers.

Chemoradiation using cisplatin-based regimens has become the standard care in the treatment of nasopharyngeal cancers. The impact of taxanes as radiosensitizing agents with concurrent chemoradiation regimens is unknown. We retrospectively evaluated the efficacy and tolerability of weekly cisplatin + docetaxel combination with chemoradiation in locally advanced nasopharyngeal cancers. Forty-two patients with locally advanced nasopharyngeal cancers (59.5% stage IV, 23.3% stage III, and 16.7% stage II) were assessed retrospectively. Total radiation dose to the planning target volume of gross disease (primary and/or node) was 70 Gy/35 fractions, 5 fractions per week. Minimum doses of 60 Gy and 50 Gy were administered to planning target volume of elective high-risk and low-risk disease, respectively. Chemotherapy consisted of weekly cisplatin (20 mg/m(2)) + docetaxel (20 mg/m(2)) concurrently with radiotherapy. The median age of the patients was 46.5 years (range, 17-79). Objective response rate was 86%. The 4-year progression-free survival and overall survival were 65.4% and 91.3%, respectively. The most common grade 3 and 4 toxicities were mucositis (48%), nausea (22%), neutropenia (12%), dermatitis (5%), fatigue (5%) and weight loss (5%). Weekly cisplatin and docetaxel concurrent with radiotherapy for locally advanced nasopharyngeal cancers was found tolerable with a high efficacy.

Induction Chemotherapy Followed by Concurrent Chemoradiation versus Concurrent Chemoradiation Alone in the Definitive Management of p16-positive Oropharyngeal Cancer with Low-neck or N3 Disease

The role of induction chemotherapy (ICT) in addition to concurrent chemoradiation (CCRT) in the definitive management of locally advanced oropharyngeal cancer is controversial. At our institution, certain patients with low-neck (level IV and/or Vb) or N3 lymphadenopathy are given ICT prior to CCRT at the discretion of the treating physicians with the objective of lowering the risk of distant failure. We compared the outcomes of these patients to their counterparts who received upfront CCRT alone. A retrospective review was conducted from June 2006 through June 2015. Out of 548 patients with locally advanced p16-positive oropharyngeal cancer, 88 were identified with low-neck and/or N3 disease. Among these patients, 44 received upfront CCRT, and 44 received ICT followed by CCRT. Upfront CCRT regimens included triweekly Cisplatin (43%), triweekly Carboplatin (32%), Cetuximab (14%), and weekly Cisplatin (11%). ICT regimens were Docetaxel and platinum based chemotherapy with (89%) or without 5-fluorouracil (11%) followed by CCRT using weekly Carboplatin (61%), triweekly Carboplatin (18%), weekly Cisplatin (11%), triweekly Cisplatin (7%), or Cetuximab (2%). All patients were planned for 70 Gy with intensity-modulated radiotherapy. Pathology review was performed of all cases with standardized p16 reporting. Median follow-up for surviving patients was 45 [13-115] months. Median age was lower in the ICT group compared to the CCRT group, 56 vs. 61, respectively (P = 0.02), with T stage, N stage, and rates of low-neck disease similar between the two groups. Compared to CCRT alone, ICT followed by CCRT was associated with a significant improvement in the rate of distant metastases (DM) (3-year: 18% vs. 37%; P = 0.01), progression-free survival (PFS) (3-year: 74% vs. 49%; P = 0.008), and overall survival (OS) (3-year: 82% vs. 67%; P = 0.05). No difference in locoregional failure was observed (3-year: 14% for both arms). Patients in the upfront CCRT group were more likely to require a feeding tube compared to the ICT group (27% vs. 57%; P = 0.005). Among ICT patients, 75% received 3 cycles of ICT with the remaining 25% receiving only 2 cycles either due to treatment-related toxicities, performance status, or suboptimal response to ICT. In this cohort of p16-positive oropharyngeal cancer patients with low-neck and/or N3 disease at high risk of distant failure, ICT followed by CCRT demonstrated a statistically significant reduction in DM which translated into an improvement in PFS and OS over upfront CCRT alone. Future randomized studies should concentrate on patients at the highest risk of developing distant metastases in order to assess the potential benefit of ICT in addition to CCRT in this population. Less intensive CCRT regimens employed in patients receiving ICT may have led to decreased rates of feeding tube placements compared to that observed in CCRT alone patients.

Comparison of three different concurrent chemoradiation regimens for treatment of laryngeal cancer.

During last decades, laryngeal organ preservation strategies have emerged. The data about the oncological outcomes mainly come from multi-institutional prospective studies. In this study, we aimed to determine the oncological outcomes of different organ preservation regimens applied in routine practice. Patients who had definitive concurrent chemoradiation (CRT) for treatment of laryngeal cancer between January 2001 and June 2013 were retrospectively reviewed. There were 139 subjects who met the inclusion criteria. Three groups were defined: group A (n=59) consisted of subjects who had concurrent cisplatin and radiotherapy (RT), group B (n=47) consisted of subjects who had cisplatin/docetaxel-based concurrent CRT, and group C (n=33) had induction chemotherapy before concurrent cisplatin and RT. The Kaplan-Meier estimated 5-year overall survival, disease-specific survival, disease-free survival, and local recurrence-free survival (LRFS) rates for the whole study group were 66.5, 69.2, 69.6, and 88.9%, respectively. None of these survival rates were statistically different when the treatment arms were compared. The 3- and 5-year LRFS rates were significantly lower in subjects with a T4a tumor (p=0.030). According to our results, the oncological outcomes of three different platinum-based concurrent chemotherapy schemes were similar and high local control rates could be achieved with the use of these protocols. Neoadjuvant chemotherapy before concurrent CRT was not superior to conventional concurrent treatment.

Radiation fosters dose-dependent and chemotherapy-induced immunogenic cell death

Established tumors are typified by an immunosuppresive microenvironment. Countering this naturally occurring phenomenon, emerging evidence suggests that radiation promotes a proimmunogenic milieu within the tumor capable of stimulating host cancer-specific immune responses. Three cryptic immunogenic components of cytotoxic-agent induced cell death—namely, calreticulin cell surface exposure, the release of high mobility group box 1 (HMGB1) protein, and the liberation of ATP—have been previously shown to be critical for dendritic cell (DC) activation and effector T-cell priming. Thus, these immune-mobilizing components commonly presage tumor rejection in response to treatment. We initially set out to address the hypothesis that radiation-induced immunogenic cell death (ICD) is dose-dependent. Next, we hypothesized that radiation would enhance chemotherapy-induced ICD when given concomitantly, as suggested by the favorable clinical outcomes observed in response to analogous concurrent chemoradiation regimens. Thus, we designed an in vitro assay to examine the 3 hallmark features of ICD at clinically relevant doses of radiation. We then tested the immunogenic-death inducing effects of radiation combined with carboplatin or paclitaxel, focusing on these combinations to mimic chemoradiation regimens actually used in clinical trials of early stage triple negative [NCT0128953/NYU-10–01969] and locally advanced [NYU-06209] breast cancer patients, respectively. Despite the obvious limitations of an in vitro model, radiotherapy produced both a dose-dependent induction and chemotherapeutic enhancement of ICD. These findings provide preliminary evidence that ICD stimulated by either high-dose radiotherapy alone, or concurrent chemoradiation regimens, may contribute to the establishment of a peritumoral proimmunogenic milieu.

Abstract P5-14-08: Prospective phase II study of concurrent capecitabine and radiation demonstrates futility in triple negative chemo-resistant breast cancer

Abstract Background: Capecitabine is an established radiosensitizer in rectal and other cancers. We conducted a prospective single arm phase II study to examine the response rate of gross chemo-refractory breast cancer treated with concurrent capecitabine and radiotherapy. Methods: Patients who had inoperable or marginally operable gross disease in the breast and/or lymph node(s) after chemotherapy or gross disease on the chest wall or in the regional lymphatics after mastectomy were eligible. Patients 1-9 received capecitabine 825 mg/m2 BID daily beginning on the first day of radiotherapy. Excess grade 3 toxicity (%) was observed; the protocol was amended and subsequent patients received drug only on radiation treatment days. Radiation dose was at the discretion of the treating physician (50Gy-72 Gy, with no more than 2.5 Gy/fraction). Response was assessed by a single physician using paired radiation planning CTs (pretreatment and on-treatment after 45 Gy). Clinical correlation to all other available imaging was also made. Kaplan-Meier curves were used to estimate overall survival (OS) and local recurrence-free survival (LRFS). Circulating tumor cells (CTCs) in blood were examined in consenting patients. Results: The trial was stopped early after an unplanned interim analysis prompted by slow accrual suggested futility independent of response. From 2009-2012, 32 patients were accrued; 26 completed protocol specific treatment (17 post-mastectomy radiation with gross nodes, 4 pre-op, 5 aggressive palliation) and are included in this analysis. Median follow up was 7.3 months (interquartile range 6.7 – 17.4). Nineteen patients (73%) had a partial or complete response. Fourteen patients (53.9%) experienced at least one grade 3 non-dermatitis toxicity including 7/9 treated with continuous dosing. Four inoperable patients were treated with pre-op radiation therapy and 3 converted to operable. None achieved a pCR or near pCR. One-year actuarial OS was 52%. There was no difference in OS comparing among PMRT vs. preoperative or palliative RT (P = 0.90). One-year actuarial local recurrence free survival among PMRT patients was 38%. Ten patients had triple negative (TN) receptor status. There was no difference in radiation response by receptor status (P = 0.56); however, treatment was deemed subjectively futile (i.e., converted to operable but death secondary to new widespread M1 disease immediately post-op) in 9 of the 10 patients with TN disease versus 6 of the 16 patients with non-TN disease (P = 0.014). Median OS and 1-yr actuarial OS, among non-TN vs. TN patients were not reached vs. 6.1 months and 77% vs. 10% (P &amp;lt; 0.001), respectively. Eight/fifteen patients tested were positive for CTCs. CTCs did not correlate to receptor status, futility of RT or OS. Conclusions: Capecitabine can be safely administered as a daily concurrent chemoradiation regimen with weekend holidays. However, in this small, prospective and selected cohort, concurrent chemoradiation with capecitabine was futile among patients with TN breast cancer. Alternative strategies are urgently needed in TN patients. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P5-14-08.

Efficacy and safety of concurrent chemoradiotherapy with cisplatin and docetaxel in patients with locally advanced nasopharyngeal cancers

Chemoradiation using cisplatin-based regimens has become the standard care in the treatment of nasopharyngeal cancers. The impact of taxanes as radiosensitizing agents with concurrent chemoradiation regimens is unknown. We retrospectively evaluated the efficacy and tolerability of weekly cisplatin + docetaxel combination with chemoradiation in locally advanced nasopharyngeal cancers. Forty-two patients with locally advanced nasopharyngeal cancers (59.5% stage IV, 23.3% stage III, and 16.7% stage II) were assessed retrospectively. Total radiation dose to the planning target volume of gross disease (primary and/or node) was 70 Gy/35 fractions, 5 fractions per week. Minimum doses of 60 Gy and 50 Gy were administered to planning target volume of elective high-risk and low-risk disease, respectively. Chemotherapy consisted of weekly cisplatin (20 mg/m(2)) + docetaxel (20 mg/m(2)) concurrently with radiotherapy. The median age of the patients was 46.5 years (range, 17-79). Objective response rate was 86%. The 4-year progression-free survival and overall survival were 65.4% and 91.3%, respectively. The most common grade 3 and 4 toxicities were mucositis (48%), nausea (22%), neutropenia (12%), dermatitis (5%), fatigue (5%) and weight loss (5%). Weekly cisplatin and docetaxel concurrent with radiotherapy for locally advanced nasopharyngeal cancers was found tolerable with a high efficacy.

A phase III randomized trial of two cisplatin-based concurrent chemoradiation (CCRT) regimens for locally advanced head and neck squamous cell carcinoma (LAHNSCC).

6035 Background: Excellent outcomes have been reported using both single and multiagent CCRT in LAHNSCC. This trial compares a 5FU/cisplatin regimen to single agent cisplatin CCRT. Methods: Patients (pts) with previously untreated stage III-IV, M0, LAHNSCC of the larynx, oropharynx (OP), oral cavity or hypopharynx received definitive once or twice daily radiation (70-74.4 Gy) and were randomized between concurrent chemotherapy with either Arm A: cisplatin 100mg/m2 on days 1, 22 and 43 or Arm B: cisplatin (20mg/m2/day) and 5-FU (1000mg/m2/day) as continuous 96 hour infusions weeks 1 and 4. ECOG performance status ≤ 1, and adequate renal, liver and marrow function were required for entry. The primary endpoint was recurrence free survival (RFS). Results: Between 2/2008 and 10/2011, 69 pts were enrolled. An accrual of 126 pts was planned in order to demonstrate an improvement in 2-year RFS from 55% to 75%. The study was closed prematurely when a scheduled interim analysis confirmed markedly better outcomes in both arms and the futility of further comparison. Pt and tumor characteristics were well balanced in both arms. OP cancer was diagnosed in 83% of pts; 86% of the OP cancers were HPV/p16+. With a median follow up of 29.4 months, 2 yr Kaplan-Meier outcome estimates were similar between arms (Table). Pts on Arm A experienced more nephrotoxicity (26% vs. 3%; p=0.007) and ototoxicity (11% vs. 0%; p=0.042), but less Grade ≥2 radiation dermatitis (43% vs. 68%; p=0.038), neutropenia &lt;1000/mm3 (34% vs. 65%; p=0.012), and unplanned hospitalization (43% vs. 68% p=0.038). Treatment outcomes were inferior and feeding tube requirements greater in the HPV/p16 negative and actively smoking pts. Conclusions: Although these CCRT regimens produced similar outcomes, their toxicity profiles proved different and may serve to inform individual pt treatment. Tobacco use and HPV status had far greater impact on treatment outcomes than did the CCRT regimen. Clinical trial information: NCT00608205. [Table: see text]

Efficacy and Safety of Concomitant Chemoradiotherapy with Cisplatin and Docetaxel in Patients with Locally Advanced Squamous Cell Head and Neck Cancers

Chemoradiation (CRT) using cisplatin-based regimens has become the standard of care in the treatment of squamous cell head and neck cancers (SCHNC). The impact of taxanes as radiosensitizing agents with concurrent CRT regimens is unknown. We therefore retrospectively evaluated the efficacy and tolerability of a weekly cisplatin+docetaxel combination with CRT in locally advanced SCHNC. Sixty-six patients with locally advanced SCHNC (39.4% stage IV, 53% stage III, and 7.6% stage II) were assessed retrospectively. Total radiation dose to the PTV of gross disease (primary and/or node) was 70 Gy/ 35 fractions, 5 fractions per week. Minimum doses of 60 Gy and 50 Gy were administered to PTVs of elective high risk and low risk disease, respectively. Chemotherapy (CT) consisted of weekly cisplatin (20 mg/m2) +docetaxel (20 mg/m2) concurrently with RT. The median age of the patients was 58 years (range, 32-77). Objective response rate was 83.3%. The 2-year progression-free survival (PFS) and overall survival (OS) were 75.7% and 78.3%, respectively. The most common grade 3 and 4 toxicities were mucositis (36.4%), nausea and vomiting (12.1%), neutropenia (4.5%). Weekly cisplatin and docetaxel concurrent with RT for locally advanced SCHNC was found tolerable with high efficacy.

Locally advanced non–small cell lung cancer: What is the optimal concurrent chemoradiation regimen?

The optimal chemoradiation regimen for patients with locally advanced non-small cell lung cancer (NSCLC) has yet to be defined. Disease and patient heterogeneity prevent a "one size fits all" approach to treatment. Concurrent chemoradiation up front is the definitive strategy for patients with unresectable stage III NSCLC; the addition of consolidation chemotherapy following definitive treatment has produced conflicting results with respect to overall survival. Biologic therapies have yet to show value as add-on treatment to chemoradiation.

53rd ASTRO annual meeting

Leonard Gunderson (Scotsdale, AZ, USA) and colleagues presented long-term data from the RTOG 98-11 trial, which compared two concurrent chemoradiation regimens—45–59 Gy with either fluorouracil and mitomycin or fluorouracil and cisplatin—for the treatment of patients with anal carcinoma. 649 of the 682 patients who were enrolled in this study were available for analysis; both 5-year disease-free survival and overall survival were better in the fluorouracil and mitomycin group than in the fluorouracil and cisplatin group (5-year disease-free survival 67·8% vs 57·8%, p=0·006 and 5-year overall survival 78·3% vs 70·7%, p=0·026). These data indicate that concurrent chemoradiotherapy with fluorouracil and mitomycin should remain the standard of care for patients with anal cancer.