Concurrent Chemotherapy Group Research Articles

The effect of sex and BMI on outcomes in patients with metastatic non-small cell lung cancer treated with immunotherapy.

e21085 Background: Recent studies suggest that among non-small cell lung cancer (NSCLC) patients treated with immunotherapy (IT), those who are male and/or have higher body mass index (BMI) benefit most; however, the role of other factors such as pretreatment weight loss is not clear. We conducted a retrospective study to further characterize the relationship between sex, BMI and response to IT in NSCLC. Methods: Patients with stage IV NSCLC treated with IT between 2017 and 2019 at UPMC Hillman Cancer Center were included. Demographic and clinical data were obtained from medical records. Chi-square test was used to compare baseline patient characteristics, best response (CR, PR and SD vs. PD), and presence of immune-related adverse events (iRAEs) between BMI and sex categories. Cox proportional hazards models were used to assess the effect of BMI and sex on progression free survival (PFS) and overall survival (OS). Analyses were conducted overall as well as stratified by treatment regime (1st line monotherapy, non-1st line monotherapy, and concurrent chemotherapy). Results: The study population consisted of 297 patients; 50.2% female (N=149), 87.8% white (N=261), and mean age at IT initiation 68 yrs (range: 36-91 yrs). Median follow-up time: 21 months. At IT initiation, 27 patients were underweight (BMI <18.5), 107 normal weight (BMI 18.5-24.9), 96 overweight (BMI 25-29.9), and 67 obese (BMI ≥30). Among underweight patients, weight loss pretreatment (≥10 lbs) was significantly more common ( P=0.02), and response to IT significantly worse (33% vs 61% good response; P=0.005) compared to those with BMI ≥18.5. No significant difference in response was observed between normal, overweight and obese patients, nor between men and women. The presence of iRAEs did not differ by BMI or sex. Females had better OS than males [HR (95%CI): 0.65 (0.47-0.90)] but PFS was similar. In stratified analyses, better OS among females was limited to the concurrent chemotherapy group [0.52 (0.30-0.92)]. Overall, underweight patients had worse OS than those with BMI ≥18.5 [1.71 (1.01-2.92)]; this was not significant after adjusting for pretreatment weight loss [1.48 (0.87-2.53)]. No difference was observed in OS and PFS between normal, overweight and obese patients. In stratified analyses, underweight individuals had worse OS [4.12 (1.55-10.94)] and PFS [3.87 (1.44-10.38)] than those with BMI ≥18.5 when treated with 1st line monotherapy. Weight loss pretreatment was independently associated with worse OS [2.20 (1.51-3.20)] and PFS [1.47 (1.05-2.05)]. Conclusions: In contrast to prior reports, NSCLC patients receiving IT did not benefit from higher BMI or male sex. Females treated with concurrent chemotherapy had improved OS, and pretreatment weight loss was an indicator of poor prognosis. Further study is required to understand the pathobiology behind these predictors.

A retrospective study of postoperative radiotherapy for locally advanced esophageal squamous cell carcinoma.

The optimal therapeutic strategy in locally advanced esophageal squamous cell carcinoma (ESCC) primarily treated by surgery remains unknown. This study was designed to evaluate the impact of postoperative chemoradiotherapy and postoperative sequential chemoradiotherapy on survival in this population. The study included a total of 228 consecutive patients who underwent radical esophagectomy and were confirmed to have stage pT3-4 or pN+ ESCC from September 2011 to September 2017 at our institution. All patients received postoperative radiotherapy with or without concurrent or sequential chemotherapy after esophagectomy. Univariate and multivariate analyses were used to compare the survival of patients with postoperative radiotherapy, postoperative concurrent chemoradiotherapy, and postoperative sequential chemoradiotherapy. After a median follow-up of 52 months, the 3- and 5-year overall survival (OS) rates were 70.2% [95% confidence interval (CI), 63.7-76.7%] and 62.2% (95% CI, 54.6-69.8%), respectively. The disease-free survival (DFS) rates at 3 and 5 years were 65.2% (95% CI, 58.7-71.7%) and 55.2% (95% CI, 47.6-62.8%), respectively. The 3- and 5-year locoregional recurrence-free survival (LRFS) rates were 65.1% (95% CI, 58.4-71.8%) and 55.5% (95% CI, 47.7-63.3%). Of the 228 patients, 38 (16.7%) had distant metastases. Subgroup analysis showed that being male and having a higher T stage were independent poor prognostic factors for OS and DFS in patients with pN+ or stage III + IVA ESCC. The results also showed that in patients with stage III + IVA ESCC, the DFS of the patients in the concurrent chemotherapy (CCT) group was improved compared with that in the no CCT group [hazard ratio (HR), 0.551; 95% CI, 0.323-0.938; P=0.028]. Multivariate analysis showed that sequential chemoradiotherapy was associated with poor LRFS (HR, 2.312; 95% CI, 1.078-4.959; P=0.031), especially in stage T3-4 patients, and it was also related to the poor DFS (HR, 1.781; 95% CI, 1.086-2.921; P=0.022) in patients with stage T3-4 ESCC. In patients with locally advanced ESCC, those who underwent sequential chemoradiotherapy had a worse LRFS. Postoperative concurrent chemoradiotherapy was the most effective adjuvant therapy for resected stage III-IVA ESCC. In addition, being male, having a higher T stage, and being node-positive were independent poor prognostic factors for OS and DFS.

Necessity of concurrent chemotherapy in N2‐3 nasopharyngeal carcinoma treated with neoadjuvant chemotherapy of ≥3 cycles followed by intensity‐modulated radiotherapy

Concurrent chemotherapy (CCT) is used in locally advanced nasopharyngeal carcinoma (NPC) for improved local control, which could also be achieved by intensity‐modulated radiotherapy (IMRT). And for N2‐3 NPC, distant metastasis is the more important cause of death. This study aims to evaluate the value of CCT in N2‐3 NPC when neoadjuvant chemotherapy (NACT) of sufficient cycles is performed to eradicate distant metastasis. It enrolled 959 patients diagnosed with TxN2‐3M0 NPC from July 2011 to December 2015 and treated with NACT of 3‐4 cycles and IMRT. A propensity score matching (PSM) was made between patients treated with and without CCT (called the CCT and non‐CCT groups, respectively), using a series of clinical characteristics (age, gender, T stage, N stage, NACT regimen, and EBV DNA) as covariates. After PSM, the two groups of patients were compared on survivals and acute toxicities. The results indicated that no difference was seen in the overall, disease‐free, recurrence‐free or metastasis‐free survivals between the two groups. But compared with the CCT group, the non‐CCT group had a lower patient proportion of myelosuppression, nausea/vomiting, oral mucositis, cervical dermatitis, xerostomia, and grade 3/4 myelosuppression and oral mucositis (all P values were <0.001). Hence, CCT appeared to bring more acute toxicities, instead of survival benefit, to N2‐3 NPC patients treated with NACT of ≥3 cycles and IMRT. It should be used with cautions in these patients.

Comparative analysis between induction chemotherapy combined with concurrent chemoradiotherapy and chemoradiotherapy alone for thoracic esophageal squamous cell carcinoma

Objective To compare the clinical efficacy and safety between induction chemotherapy (IC) followed by concurrent chemotherapy (CRT) and CRT alone in patients with inoperable thoracic esophageal squamous cell carcinoma (ESCC). Methods Between 2002 and 2015, clinical data of 267 thoracic ESCC patients undergoing definitive CRT based on docetaxel combined with cisplatin were retrospectively analyzed. Through a matched case-control study, 85 patients receiving IC combined with CRT were matched to those undergoing CRT alone at a ratio of 1vs.1, according to age, gender, performance status, tumor location, tumor length, and TNM staging as the matching factors. Clinical efficacy and safety between two groups were statistically compared. Kaplan-Meier survival analysis was used to analyze the survival. The log-rank test was adopted to examine within-group differences. The Cox regression model was used for multivariate analysis. Results The median follow-up time for 170 patients was 18 months (range, 3-72 months). The overall objective response rates in the IC and CRT groups were 74.1% and 58.8%(P=0.035). The 3-year overall survival (OS) and progress-free survival (PFS) rates in the IC group were 44.2% and 34.8%, significantly higher than 29.7% and 15.4% in the CRT group (P=0.028, P=0.015). Subgroup analysis revealed that patients responsive to IC obtained significantly better OS (P=0.002), PFS (P=0.001), and local recurrence-free survival (LRFS)(P=0.002) compared with the IC non-responder, whereas the distant metastasis-free survival (DMFS) did not significantly differ (P=0.166). The incidence rate of grade 3–4 leukopenia in the IC group was significantly higher than that in the CRT group (38.8% vs. 24.7%, P=0.048). Multivariate analysis revealed that age and the addition of IC were independent prognostic factors for OS (P=0.003, 0.016). Conclusions Compared with concurrent CRT, IC in combination with CRT can yield better short-term efficacy and longer survival for ESCC patients. The risk of hematological toxicity in the IC group is relatively higher but tolerable. Prospective randomized trials are required to confirm the clinical efficacy and safety of IC for thoracic ESCC patients. Key words: Esophageal neoplasms/concurrent chemoradiotherapy; Induction chemotherapy; Prognosis

Efficacy, toxicity and prognosis analysis of three-dimensional conformal radiotherapy combined with concurrent chemotherapy for locally advanced cervical cancer

Objective To explore the efficacy, toxicity and prognosis of three-dimensional conformal radiotherapy combined with concurrent chemotherapy for locally advanced cervical cancer. Methods From January 2014 to January 2015, 96 patients with locally advanced cervical cancer in Yuncheng Central Hospital were selected and randomly divided into radiotherapy group and concurrent chemoradiotherapy group according to the digital table, with 48 cases in each group.The radiotherapy group received CT based three-dimensional conformal radiotherapy and three-dimensional 192Ir after loading irradiation technology, the concurrent chemotherapy group received docetaxel plus cisplatin chemotherapy synchronous three-dimensional conformal radiotherapy and three-dimensional 192Ir after loading irradiation technology.The clinical effect, 2-year survival rate, liver function injury, leukopenia and incidence of side effects, survival of patients and Karnofsky score before and after treatment were compared between the two groups. Results The effective rate of chemoradiotherapy of the concurrent chemoradiotherapy group was 75.00%, which was higher than 50.00% of the radiotherapy group (χ2=4.181, P 0.05). Before treatment, the living conditions and Karnofsky score had no statistically significant differences between the two groups (all P>0.05). After treatment, the survival and Karnofsky score improved more significantly in the concurrent chemoradiotherapy group, the differences were statistically significant(all P<0.05). Conclusion The curative effect of three dimensional conformal radiotherapy combined with concurrent chemotherapy on locally advanced cervical cancer is definite, and it can improve the prognosis of patients with high safety.As to liver function damage, leukocyte depletion and other toxic side effects, there are no statistically significant differences between two groups, so it is worthy of popularizing. Key words: Cervical cancer, advanced; Three dimensional conformal radiotherapy; Concurrent chemotherapy; Toxic and side effects

Outcomes of adding induction chemotherapy to concurrent chemoradiotherapy for stage T3N0-1 nasopharyngeal carcinoma: a propensity-matched study.

ObjectiveOur objective was to examine whether adding induction chemotherapy to concurrent chemoradiotherapy improved survival in stage III nasopharyngeal carcinoma (NPC) patients, especially in low-risk patients at stage T3N0-1.Materials and methodsWe retrospectively analyzed 687 patients with stage T3N0-1 NPC treated with intensity-modulated radiation therapy (IMRT) plus concurrent chemotherapy (CC) with or without induction chemotherapy (IC). Propensity score matching (PSM) method was used to select 237 pairs of patients from two cohorts. Overall survival (OS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS), and progression-free survival (PFS) were assessed by using the Kaplan–Meier method, log-rank test, and Cox regression analysis.ResultsNo significant survival differences were observed between IC plus CC and CC cohorts with similar 4-year OS (91.7% vs 92.6%, P=0.794), LRFS, (92.7% vs 96.8%, P=0.138), DMFS (93.5% vs 94.3%, P=0.582), and PFS (87.5% vs 91.1%, P=0.223). In a univariate analysis, lower Epstein–Barr virus deoxyribonucleic acid (EBV DNA; <4,000 copies/mL) significantly improved 4-year DMFS (95.5% vs 91.6%, P=0.044) compared with higher EBV DNA (≥4,000 copies/mL). No factors were associated with 4-year OS, LRFS, DMFS, and PFS in a multivariate analysis. IC plus CC group experienced higher rates of grade 3–4 leucopenia (P<0.001) and neutropenia (P<0.001).ConclusionThe addition of IC to CC in stage T3N0-1 NPC patients treated with IMRT did not significantly improve their survival. The IC group experienced higher rates of grade 3–4 hematological toxicities. Therefore, further investigation is required.

An analysis of efficacy of intensity-modulated radiotherapy with concurrent chemotherapy for stage T1-2N1 nasopharyngeal carcinoma

Objective To retrospectively analyze the efficacy and toxicity of intensity-modulated radiotherapy (IMRT) alone and IMRT with concurrent chemotherapy (CRT) in the treatment of early-stage nasopharyngeal carcinoma (NPC) using pairwise group comparison. Methods A total of 98 patients with stage T1-2N1M0 NPC were treated with IMRT alone or CRT from 2009 to 2010, and 39 pairs out of them were selected for comparison of efficacy and toxicity. The survival rates were calculated using the Kaplan-Meier method and analyzed using the log-rank test. Results The 3-year follow-up rate was 95%. There were no significant differences in the 3-year overall survival (OS), progression-free survival (PFS), local recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) rates between the IMRT alone group and the CRT group (97% vs. 95%, P=0.411; 97% vs. 92%, P=0.301; 97% vs. 97%, P=0.606; 100% vs. 92%, P=0.082). The incidence rates of leucopenia, anemia, and thrombocytopenia were significantly higher in the CRT group than in the IMRT alone group (P=0.000; P=0.000; P=0.000). There were no significant differences in the incidence rates of grade 3 oral mucositis and hearing loss between the IMRT alone group and the CRT group (26% vs. 23%, P=0.093; 41% vs. 62%, P=0.100). Conclusions CRT fails to increase the OS, PFS, and LRFS rates and reduce the DMFS rate in patients with stage T1-2N1 NPC. Moreover, CRT results in higher incidence rates of hematotoxicity, grade 3 mucositis, and hearing loss than IMRT alone. Key words: Nasopharyngeal neoplasms/intensity-modulated radiotherapy; Nasopharyngeal neoplasms/concurrent chemoradiotherapy; Prognosis

Value of postoperative radiochemotherapy for thoracic esophageal squamous cell carcinoma with lymph node metastasis

To retrospectively compare the efficacy of postoperative radiotherapy (RT) alone with that of postoperative radiotherapy with concurrent chemotherapy (CRT) for thoracic esophageal squamous cell carcinoma (EPC) with positive lymph nodes, and to evaluate the clinical value of RT + CRT. 304 EPC patients underwent esophagectomy with three-field lymph node dissection had pathological lymph node metastases, but no hematogenous distant metastasis. Among them, 140 cases underwent postoperative RT alone, and 164 cases underwent postoperative CRT. The dose of irradiation was 50 Gy, and the chemotherapy regimen was taxol and cis-platinum, and a cycle was 21 days. The 1-, 3- and 5-year total survival rates of the whole group were 90.1%, 56.6% and 43.3%, respectively, with a median survival time of 49.7 months. The 5-year overall survival rates of the CRT and RT groups were 47.4% and 38.6%, respectively (P = 0.030), with a median survival time of 53.5 and 41.7 months, respectively (P = 0.030). The overall survival rates of the patients who underwent 1, 2, 3, 4 cycles of chemotherapy were 24.4%, 53.0%, 58.1% and 43.3%, respectively (P = 0.007). Among them, the 5-year total survival rate of patients with 2-4 cycles of chemotherapy was significantly better than that of patients who underwent one cycle of chemotherapy (P = 0.001). Univariate analysis showed that number of metastatic lymph nodes, pT stage, therapeutic regimen and number of chemotherapy cycles were significantly correlated with the prognosis of the patients (P < 0.05 for all). Multivariate analysis showed that number of metastatic lymph nodes, pT stage, and number of chemotherapy cycles were independent prognostic factors of the patients (P < 0.05 for all). Early toxic effects including neutropenia, radiation esophagitis, and gastrointestinal effects were significantly more severe in the CRT group than that in the RT group (P < 0.05), however, there were no significant differences of late toxic effects between the two groups (P > 0.05). Postoperative CRT for thoracic EPC with positive lymph nodes can improve the survival rate, with tolerable adverse effects.

Multivariate Analysis of Survival, Local Control, and Time to Distant Metastases in Patients with Unresectable Non–Small-Cell Lung Carcinoma Treated with 3-Dimensional Conformal Radiation Therapy with or Without Concurrent Chemotherapy

BACKGROUND: Three-dimensional (3D) conformal radiation therapy (CRT) and chemotherapy have recently improved lung cancer management. PATIENTS AND METHODS: We reviewed outcomes in 68 patients with unresectable stage I-III non–small-cell lung cancer. Treatment consisted of 3D CRT alone or with concurrent chemotherapy (CCR). RESULTS: Concurrent chemotherapy improved survival, to a median of 17 months ± 4.9 months, compared with 8 months ± 4.1 months for the radiation therapy (RT) alone group (P = 0.0347). The 2- and 5-year survival rates were 40.3% ± 7.7% and 14.1% ± 6.4%, repectively, with CCR, compared with 19.6% ± 9.6% and 0, respectively, for RT alone. In a subgroup analysis for age > 65, patients who received CCR (n = 20) had significantly improved survival and local control (P = 0.005 and P = 0.0286, respectively). Acute esophageal toxicity Radiation Therapy Oncology Group grade ≤ 3 was significantly higher in the CCR group and correlated with the RT dose (19% in CCR vs. 0 in RT, P = 0.0234; P = 0.050). The overall incidences of esophageal and pulmonary toxicity grade ≤ 3 were 20.6% and 5.9%, respectively. CONCLUSION: Our study confirms that CCR is associated with improved survival over RT alone, with a tolerable increase in acute toxicity.

Lack of benefit of concurrent chemotherapy in patients with cervical cancer and negative lymph nodes by FDG-PET

To compare the outcome of patients with cervical cancer and negative lymph nodes by fluorodeoxyglucose-positron emission tomography (FDG-PET) treated with irradiation (RT) and concurrent chemotherapy or RT alone. This was a prospective data registry of 65 patients with cervical cancer and negative lymph nodes by whole-body FDG-PET. The tumor stage was IB2 in 11, IIB in 37, and IIIB in 17 patients. RT alone was administered to 15 and RT with concurrent weekly cisplatin to 50 patients. The 5-year overall survival estimate was 85% with RT and 81% with RT and concurrent chemotherapy (p = 0.91). The corresponding 5-year cause-specific survival estimates were 78% and 74% (p = 0.98). The differences in the sites of recurrence (pelvis vs. distant metastasis) were not statistically significant between the two groups (p = 0.77). A Cox proportional hazards model of survival outcome did not identify chemotherapy, overall treatment time, or radiation dose as statistically significant prognostic factors. Severe complications included one rectovaginal fistula, one rectal stricture requiring colostomy (both in the concurrent chemotherapy group), and one death from chemotherapy-related complications. Irradiation with concurrent cisplatin was not advantageous compared with RT alone in patients with negative lymph nodes on FDG-PET.

Stage III non-small-cell lung cancer treated with high-dose hyperfractionated radiation therapy and concurrent low-dose daily chemotherapy with or without weekend chemotherapy: retrospective analysis of 301 patients.

We investigated the outcome in patients with stage III non-small-cell lung cancer (NSCLC) treated with high-dose hyperfractionated radiation therapy (Hfx RT) and concurrent chemotherapy (CHT) consisting of carboplatin (C) and etoposide (E). During three prospective randomized phase III and one prospective phase II study enrolling a total of 536 patients, 301 patients were treated with high-dose Hfx RT (69.6 Gy) and either low-dose daily CE (50 mg each) (n = 163) or daily CE (30 mg each) accompanied by "weekend" CE (100 mg of each on Saturdays and Sundays) (n = 138). The median survival time for all 301 patients is 22 months and 5-year survival is 24%. Median local recurrence-free survival (LRFS) time is 21 months and 5-year local recurrence-free survival is 32%. The median time to distant metastasis is 25 months, and 5-year distant metastasis-free survival (DMFS) is 35%. Only the type/schedule of CHT administration did not influence overall survival, LRFS, and DMFS. On multivariate analyses using these three endpoints, age stage, interfraction interval, and type/schedule of CHT administration did not predict survival, LRFS, and DMFS, while gender, KPS, and weight loss did. Only high grade hematologic toxicity was more frequent in weekend CHT group. High dose Hfx RT and concurrent low-dose daily CE with or without weekend CE is an active treatment approach in stage III NSCLC that led to high overall survival, LRFS, and DMFS rates.