Course Of Concurrent Chemoradiotherapy Research Articles

Predictors of Tumor Dynamics Over a 6-Week Course of Concurrent Chemoradiotherapy for Glioblastoma and the Effect on Survival

We present the final analyses of tumor dynamics and their prognostic significance during a 6-week course of concurrent chemoradiotherapy for glioblastoma in the Glioblastoma Longitudinal Imaging Observational study. This is a prospective serial magnetic resonance imaging study in 129 patients with glioblastoma who had magnetic resonance imaging obtained at radiation therapy (RT) planning (F0), fraction 10 (F10), fraction 20 (F20), and 1-month post-RT. Tumor dynamics assessed included gross tumor volume relative to F0 (Vrel) and tumor migration distance (dmigration). Covariables evaluated included: corpus callosum involvement, extent of surgery, O6-methylguanine-DNA-methyltransferase methylation, and isocitrate dehydrogenase mutation status. The median Vrel were 0.85 (range, 0.25-2.29) at F10, 0.79 (range, 0.09-2.22) at F20, and 0.78 (range, 0.13-4.27) at 1 month after completion of RT. The median dmigration were 4.7 mm (range, 1.1-20.4 mm) at F10, 4.7 mm (range, 0.8-20.7 mm) at F20, and 6.1 mm (range, 0.0-45.5 mm) at 1 month after completion of RT. Compared with patients who had corpus callosum involvement (n = 26), those without corpus callosum involvement (n = 103) had significant Vrel reduction at F20 (P = .03) and smaller dmigration at F20 (P = .007). Compared with patients who had biopsy alone (n = 19) and subtotal resection (n = 71), those who had gross total resection (n = 38) had significant Vrel reduction at F10 (P = .001) and F20 (P = .001) and a smaller dmigration at F10 (P = .03) and F20 (P = .002). O6-Methylguanine-DNA-methyltransferase methylation and isocitrate dehydrogenase mutation status were not significantly associated with tumor dynamics. The median progression-free survival and overall survival (OS) were 8.5 months (95% CI, 6.9-9.9) and 20.4 months (95% CI, 17.6-25.2). In multivariable analyses, patients with Vrel ≥ 1.33 at F10 had worse OS (hazard ratio [HR], 4.6; 95% CI, 1.8-11.4; P = .001), and patients with dmigration ≥ 5 mm at 1-month post-RT had worse progression-free survival (HR, 1.76; 95% CI, 1.08-2.87) and OS (HR, 2.2; 95% CI, 1.2-4.0; P = .007). Corpus callosum involvement and extent of surgery are independent predictors of tumor dynamics during RT and can enable patient selection for adaptive RT strategies. Significant tumor enlargement at F10 and tumor migration 1-month post-RT were associated with poorer OS.

Predictors of Tumor Dynamics during a 6-Week Course of Chemoradiotherapy for Glioblastoma

Our prior imaging studies have shown geometrically meaningful inter-fraction tumor dynamics specific to glioblastoma (GBM). We aim to identify predictors associated with tumor dynamics during a 6-week course of concurrent chemoradiotherapy (CRT) for GBM. Patients enrolled in a prospective serial magnetic resonance imaging (MRI) study were reviewed. All patients were treated with 54-60 Gy in 30 fractions. The gross tumor volume (GTV) included the surgical cavity and T1c enhanced residual tumor; clinical tumor volume (CTV) included GTV with a 15mm isotropic expansion, respecting anatomical boundaries; planning target volume (PTV) was 4mm expansion. MRIs were obtained at RT planning (F0), fraction 10 (F10), and fraction 20 (F20). Tumor dynamic metrics (relative to F0) assessed included the GTV volume (Vrel), Hausdorff distance (dH) and migration distance (dM). dH is the average distance between two datasets in metric space. dM is the maximum linear displacement of the GTV in any direction. Factors to be determined associated with tumor dynamics included: age, sex, corpus callosum (CC) involvement, extent of surgery (gross total resection (GTR), subtotal resection (STR) or biopsy alone (Bx)), MGMT methylation and IDH mutation status. A total of 129 patients were reviewed. Median GTV was 20.9cc at F0, 17.6cc at F10 (Vrel 0.85), and 16.1cc at F20 (Vrel 0.78). Patients without CC involvement had more marked GTV volume reduction: Vrel 0.82 vs 1.02 with CC involvement at F10 (P = 0.05), and Vrel 0.77 vs 0.88 with CC involvement at F20 (P = 0.03). Patients with GTR (vs STR vs Bx) had more marked GTV volume reduction across all time points: Vrel 0.78, 0.85 and 1.07 respectively at F10 (P = 0.001), and Vrel 0.69, 0.80, 1.04 respectively at F20 (P = 0.001). The median dH was 8.1mm at F10 and 9.2mm at F20. Patients with CC involvement (vs without CC involvement) had a larger dH: 54% vs 25% had dH>10mm respectively at F10 (P = 0.03), and 73% vs 28% had dH>10mm respectively at F20 (P<0.005). Patients with a GTR had smaller dH at both F10 (P = 0.02) and F20 (P = 0.006). At F20, 20%, 47% and 37% of patients with GTR, STR and Bx had dH>10mm (P = 0.04). The median dM were 4.7mm at F10 and 4.7mm at F20. Patients with CC involvement (vs without CC involvement) had larger dM: 41% vs 12% had dM >10mm respectively at F10 (P = 0.01), and 45% vs 9% had dM >10mm respectively at F20 (P<0.001). Patients with GTR had smaller dM at F10 (P = 0.03) and F20 (P0.002). At F20, 0%, 25% and 19% of patients with GTR, STR and Bx had dM>10mm (P = 0.002). Age, sex, MGMT methylation and IDH mutation status were not associated with Vrel, dH and dM at F10 and F20. We identified CC involvement and extent of surgery to be associated with tumor dynamics at F10 and F20 over the course of CRT for GBM. This offers opportunities to better select patients who may benefit from earlier/ more frequent RT replan/ adaptation to ensure adequate tumor coverage, or to reduce RT toxicities.

Villoglandular Adenocarcinoma of the Uterine Cervix: A Case Report.

Cervical adenocarcinomas constitute for approximately 10%-20% of all invasive cervical cancers. Villoglandular adenocarcinomas (VGAs) are a rare subtype of cervical adenocarcinoma, representing approximately 5% of all cases of cervical adenocarcinomas. Herein, we report the case of a 49-year-old perimenopausal woman successfully treated for VGA. The patient presented to the hospital with a primary complaint of vaginal discharge persisting for 7 months with worsening symptoms. She had no underlying medical conditions or history of oral contraceptive use. A punch biopsy revealed an adenocarcinoma, and a human papillomavirus (HPV) test indicated positive for HPV-16. The patient underwent a radical hysterectomy with bilateral pelvic lymph node dissection, and a pathological diagnosis of VGA was established. After surgery, the patient underwent a 6-week course of concurrent chemoradiotherapy with cisplatin. During the 42 months of follow-up, no signs of disease recurrence or metastasis were observed. Because of the limitations of specimen acquisition, achieving a precise diagnosis through cervicovaginal cytology and punch biopsy is challenging. Instead, conization should be considered to prevent misdiagnosis.

244P Alternate-day hypofractionated radiotherapy for radical treatment of head & neck cancer during the COVID-19 pandemic: A single institute experience

Managing head and neck squamous cell carcinoma (HNSCC) requires a prolonged course of concurrent chemoradiotherapy and other supportive care measures. Such a multidisciplinary approach was significantly hampered during the emergence of the COVID-19 pandemic which necessitated divergence of health resources towards treating the infected patients thereby compromising cancer care. Therefore, we adopted an alternate-day hypofractionated radiotherapy (ADH RT) schedule, aiming to decrease patients’ hospital visits daily without compromising the oncological outcomes.

Treatment-Interval Changes in Serum Levels of Albumin and Histidine Correlated with Treatment Interruption in Patients with Locally Advanced Head and Neck Squamous Cell Carcinoma Completing Chemoradiotherapy under Recommended Calorie and Protein Provision.

Simple SummaryTreatment interruption during concurrent chemoradiotherapy (CCRT) jeopardizes the outcomes of patients with locally advanced head and neck squamous-cell carcinoma (LAHNSCC), which is associated with increased toxicity during CCRT. Nonetheless, we found that under the provision of recommended calories (25 kcal/kg/day) and protein (1 g/kg/day) throughout the treatment course, treatment-interval changes in serum albumin and histidine levels—not treatment toxicity—greatly contributed to the interruption of treatment in patients with LAHNSCC. We believe that serum levels of albumin and histidine should be integrated into the routine nutritional assessment of patients undergoing CCRT.We investigated risk factors for treatment interruption (TI) in patients with locally advanced head and neck squamous-cell carcinoma (LAHNSCC) following concurrent chemoradiotherapy (CCRT), under the provision of recommended calorie and protein intake; we also evaluated the associations between clinicopathological variables, calorie and protein supply, nutrition–inflammation biomarkers (NIBs), total body composition change (TBC), and a four-serum-amino-acid metabolite panel (histidine, leucine, ornithine, and phenylalanine) among these patients. Patients with LAHNSCC who completed the entire planned CCRT course and received at least 25 kcal/kg/day and 1 g of protein/kg/day during CCRT were prospectively recruited. Clinicopathological variables, anthropometric data, blood NIBs, CCRT-related factors, TBC data, and metabolite panels before and after treatment were collected; 44 patients with LAHNSCC were enrolled. Nine patients (20.4%) experienced TIs. Patients with TIs experienced greater reductions in hemoglobin, serum levels of albumin, uric acid, histidine, and appendicular skeletal mass, and suffered from more grade 3/4 toxicities than those with no TI. Neither increased daily calorie supply (≥30 kcal/kg/day) nor feeding tube placement was correlated with TI. Multivariate analysis showed that treatment-interval changes in serum albumin and histidine levels, but not treatment toxicity, were independently associated with TI. Thus, changes in serum levels of albumin and histidine over the treatment course could cause TI in patients with LAHNSCC following CCRT.

Impact of Frailty on Treatment Outcome in Patients With Locally Advanced Esophageal Cancer Undergoing Concurrent Chemoradiotherapy

The clinical significance of frailty status on treatment outcome in patients with esophageal cancer (EC) has been seldom explored. This study aimed to evaluate the impact of pretreatment frailty on treatment-related toxicity and survival outcome in patients with EC undergoing concurrent chemoradiotherapy (CCRT). Patients aged ≥20 years and with newly diagnosed locally advanced EC receiving neoadjuvant radiotherapy and concurrent chemotherapy with weekly administration of carboplatin and paclitaxel for 5 weeks were prospectively enrolled. A pretreatment frailty assessment was performed within 7 days before CCRT initiation. The primary endpoint was treatment-related toxicity and complications of CCRT while the secondary endpoint was overall survival. A total of 87 patients were enrolled, 41 (47%) and 46 (53%) of whom were allocated in the frail and fit group, respectively. Frail patients had a significantly higher incidence of having at least one severe hematological adverse event (63.4% vs. 19.6%, p<0.001), higher risk of emergent room visiting [relative risk 3.72; 95% confidence interval (CI)=1.39-9.91; p=0.009] and hospitalization (relative risk 3.85; 95% CI=1.03-11.2; p=0.013) during the course of CCRT, when compared to fit patients. Overall survival showed significant worsening in the frail group [adjusted hazard ratio (HR)=2.12; 95% CI=1.01-4.42; p=0.046]. Frailty is associated with increase of treatment-related toxicities and poor survival outcome in EC patients undergoing CCRT. Our study suggested that pretreatment frailty assessment is imperative to serve as a predictor and prognostic factor for all adult patients with EC undergoing CCRT.

Study of Side Effects of Patients Receiving Cisplatin in the Treatment of Cervical Cancer by Age Group

Background: Cisplatin is one of the options of chemotherapy used to treat cervical cancer. Patient can experience side effects from drugs frequently with many factors as a catalyst including the age of the patient.&#x0D; Objective: To compare the side effects of cervical cancer patients receiving concurrent chemoradiotherapy (Cisplatin) 2 rounds between patients ≤ 60 years and &gt; 60 years.&#x0D; Methods: A retrospective study, 70 cervical cancer patients undergoing concurrent chemoradiotherapy at Ramathibodi Hospital were investigated. Questionnaires about adverse effects were completed by patients at home 7 days after 1st and 2nd courses of combined therapy. The side effects of cervical cancer patients between groups was analyzed.&#x0D; Results: Of 70 patients, there were 47 patients ≤ 60 years and 23 patients &gt; 60 years. After the 1st course, life-threatening side effects occurred in 9 patient’s ≤ 60 years but none occurred in patients &gt; 60 years. Younger patients also had significant more nausea than older patients (P &lt; .05). After the 2nd course, younger patients also had significant more vomiting than older patients (P &lt; .05). The most common side effects for both age groups were fatigue and anorexia respectively.&#x0D; Conclusions: Patients younger than 60 year would experience significantly more symptoms of nausea and vomiting after the 1st and 2nd courses of concurrent chemoradiotherapy.

Predictive value and changes of miR-34a after concurrent chemoradiotherapy and its association with cognitive function in patients with nasopharyngeal carcinoma.

This study explored the changes and predictive value of miR-34a in nasopharyngeal carcinoma (NPC) after concurrent chemoradiotherapy (CCRT), and its association with cognitive function. Fifty NPC patients admitted to Shunde Hospital, and another fifty healthy individuals were assigned into treated group and control group, respectively. Patients in the treated group received 3 courses of CCRT. The relative expression of miR-34a in the two groups was detected, and the cognitive function of patients was assessed. Diagnostic and predictive values of miR-34a in advanced NPC were analyzed. The expression of miR-34a in the control group was significantly higher than that in the treated group (t=13.364, P<0.001), with an area under the curve (AUC) of 0.979. The expression of miR-34a was significantly upregulated after treatment (t=4.559, P<0.001). After treatment, there were 32 complete remission (CR) patients and 18 partial remission (PR) patients. According to efficacy, CR patients were classified as significant group and PR patients as general group. The expression of miR-34a in the significant group was higher than that in the general group before treatment (t=4.704, P<0.001), with an AUC of 0.852. The Montreal Cognitive Assessment (MoCA) score was significantly decreased after treatment (t=13.042, P<0.001). The expression of miR-34a was positively correlated with the MoCA score after treatment, that is, MoCA score gradually increased with the upregulation of miR-34a expression (r=0.379, P=0.006). There is a positive correlation between miR-34a and cognitive function of patients. Moreover, the expression of miR-34a can be used as a potential predictor of the efficacy of CCRT in patients with NPC.

Cardiac Irradiation Predicts Activity Decline in Patients Receiving Concurrent Chemoradiation for Locally Advanced Lung Cancer

Many patients with lung cancer are inactive due to their disease and underlying comorbidities, and activity levels can decline further during cancer therapy. Here we explore dosimetric predictors of activity decline in a cohort of patients who underwent continuous activity monitoring during definitive concurrent chemoradiotherapy (CRT) for locally advanced lung cancer. We identified patients who participated in prospective clinical trials involving the use of a commercial fitness tracker throughout the course of CRT. For each patient, we applied linear regression to log-transformed daily step counts to compute the weekly rate of activity change from 1 week before radiation therapy (RT) initiation to 2 weeks after RT completion. Clinical and dosimetric factors were tested as predictors of activity change using linear regressions. Forty-six patient met the eligibility criteria. Median age was 66 years (range, 38-90). Pretreatment Eastern Cooperative Oncology Group performance status was 0, 1, and 2 for 17%, 70%, and 13%, respectively. Mean lung dose ranged from 5.0 to 23.5 Gy, mean esophagus dose from 1.1 to 39.6 Gy, and mean heart dose from 0.6 to 31.5 Gy. Median daily step count average was 5861 (interquartile range, 3540-8282) before RT and 3422 (interquartile range, 2364-5395) 2 weeks after RT completion. Rate of activity change was not significantly associated with age, performance status, or mean RT dose received by lungs or esophagus. In multivariate analysis, mean heart dose was significantly associated with rate of activity decline, with a 3.1% reduction in step count per week for every 10 Gy increase in mean heart dose (95% confidence interval: 0.5-5.7, P = .023). Extent of cardiac irradiation is associated with the rate of physical activity decline during CRT for lung cancer. Our novel finding contributes to the growing body of evidence that adverse effects of cardiac irradiation may be manifested at early time points.

Daily step counts to predict hospitalizations during concurrent chemoradiotherapy for solid tumors.

293 Background: Wearable activity trackers could be useful tools in cancer care. Potential gains include better selection of patients fit for aggressive treatment, improved evaluation of patients during treatment, and provision of enhanced supportive care for patients. In a pilot study, low daily step counts were associated with increased risk for hospital admission during concurrent chemoradiotherapy for solid tumors of the head/neck, lung, or gastrointestinal tract. Here we seek to refine those findings using a larger patient cohort. Methods: Study subjects wore a commercial fitness tracker during a course of concurrent chemoradiotherapy. Patient characteristics, daily step counts, and hospital admissions between the initiation and completion of radiotherapy were tabulated. EORTC QLQ-C30 questionnaires were completed weekly, and summary QoL (range: 0-100) for each subject and week were calculated. Cox regression models with time-dependent and time-fixed covariates were used to identify predictors of first hospital admission during the radiotherapy course. Results: 188 subjects from three trials met inclusion criteria. The most common cancer diagnoses were head and neck (31%), lung (28%), and a gastrointestinal (30%, most commonly rectal [10%] or esophageal [6%]). Median age was 61 (range: 27-90). Baseline ECOG performance status was 0 for 46% of subjects, 1 for 47%, and 2 for 7%. The median patient compliance of wearing activity trackers and contributing data was 98%; 38subjects (20%) were hospitalized during the radiotherapy course. Cox regression demonstrated a 36% reduction in the risk of hospitalization for every 1000 daily steps (averaged over the past 3 days; hazard ratio 0.62, 95% confidence interval 0.48-0.81, p=0.0005). Diagnosis, age, baseline performance status, and QoL score were not statistically significant predictors of hospitalization risk. Conclusions: Continuous activity monitoring with wearable devices during concurrent chemoradiotherapy is feasible. We have validated daily step counts as dynamic predictors of hospitalization risk during treatment. Interventional trials should leverage activity data to optimize supportive care during cancer therapy.

Nutritional Status During Concurrent Chemoradiotherapy (CCRT) Is Critical for Survival in Patients with Locally Advanced Unresectable Esophageal Cancer

Weight loss is commonly presented in patients with locally advanced esophageal cancer (EC) during their treatment course. However, an optimal goal of nutrition support for patients with locally advanced EC remains unclear. This study was conducted to evaluate the association between nutritional status change during CCRT and survival outcome for patients with cT4b EC without baseline underweight (body mass index (BMI) ≥ 18.5 kg/m2). A retrospective review of 1120 newly diagnosed EC patients at our institution between 2009 and 2017 was conducted. One hundred and twenty-three T4b thoracic EC patients without distant metastasis who underwent curative CCRT were identified. Within this population, 101 patients without baseline underweight were included in this study. Clinical factors, body weight, and BMI were recorded before CCRT started. Nutritional statuses based on weight change during CCRT course were also measured and recorded for analysis. Survival analysis was calculated using Kaplan-Meier method with log-rank test, and prognostic factors were examined by Cox proportional hazards model. The mean pretreatment BMI of this cohort was 22.64 ± 3.11 kg/m2. The median percentage of weight loss during CCRT was 4.85% (Interquartile range (IQR) = 2.32%-8.76%) and the median time to reach the lowest weight after CCRT was 34 days (IQR = 23-41 days). The median overall survival (OS) of the entire cohort was 15.5 months. Univariate analysis revealed that better nutritional status, defined as weight loss ≤ 4%, during CCRT was a significant prognostic factor for OS. The median OS time for patients with weight loss ≤ 4% and weight loss > 4% were 24.9 months and 12.3 months, respectively (p = 0.007). Multivariate analysis further confirmed that weight loss ≤ 4% during CCRT was an independent prognostic factor for OS with a hazard ratio of 1.950 (95% Confidence Interval : 1.198-3.174, p = 0.007). Our study revealed that better nutritional status during CCRT course is associated with better survival for patients with unresectable locally advanced EC. This index, weight loss ≤ 4%, could be served as a goal for nutrition support in this group of patients during their CCRT course in the future. Further prospective studies are warranted to validate our findings.Abstract 2423; Table 1CharacteristicsMedian Survival (month)Univariable AnalysisMultivariable AnalysisHR95% CIp ValueHR95% CIp ValueWeight Loss≤ 4%24.91.9551.206-3.1690.007*1.9981.229-3.2490.005*> 4%12.3Salvage SurgeryYes38.22.0661.244-3.4320.005*1.9001.125-3.2080.016*No10.4Age≤ 6516.62.3211.373-3.9230.002*1.8631.087-3.1910.024*> 659.6Clinical N stage≤ 153.41.9081.148-3.1690013*1.8321.092-3.0740.022*> 113.2HR, Hazard Ratio; CI, Confidence Interval. Open table in a new tab

Prognostic Value of Delta Inflammatory Biomarker-based Nomograms in Patients with Inoperable Locally Advanced NSCLC

Inflammation plays critical roles in tumor growth and progression, and can be adversely affected by chemotherapy and radiotherapy. However, there have been few studies on the prognostic value of delta (Δ) inflammatory biomarkers before and after chemoradiotherapy in patients with locally advanced non-small-cell lung cancer (LA-NSCLC). In this study, pre/post-treatment and Δ inflammatory biomarkers of 370 patients who were diagnosed as having inoperable LA-NSCLC in Shandong Cancer Hospital between January 2005 and January 2016 were analyzed. Nomograms were then established for predicting prognosis. Median overall survival (OS) and progression free survival (PFS) for all patients were 28.1 (range 1.9–129.0) months and 11.1 (range 1.7–58.7) months, respectively. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) significantly increased and the lymphocyte-to-monocyte ratio (LMR) significantly decreased during the concurrent chemoradiotherapy course (P<0.001, P<0.001, and P<0.001, respectively). Multivariate analysis revealed that pre-LMR, ΔNLR, and minimum absolute lymphocyte counts were independent predictors of OS (P=0.027, P=0.012, and P=0.015, respectively) and post-LMR, post-NLR, and ΔNLR were independent predictors of PFS (P=0.014, P=0.001, and P=0.036, respectively). Nomograms for OS and PFS were established by combining all significant inflammatory markers and clinicopathological characteristics. The concordance indexes for OS and PFS were 0.709 and 0.688, respectively. Post-treatment and Δ inflammatory biomarkers may have more prognostic significance than baseline measurements of inflammatory biomarkers in LA-NSCLC patients. The proposed nomograms based on the dynamic inflammatory biomarkers and clinicopathological factors are practical and widely available for evaluating the prognosis of patients with inoperable LA-NSCLC.

Home enteral nutrition may prevent myelosuppression of patients with nasopharyngeal carcinoma treated by concurrent chemoradiotherapy.

The aim of this study is to assess the effect of home enteral nutrition (HEN) on the myelosuppression of patients with nasopharyngeal cancer (NPC) during the course of concurrent chemoradiotherapy (CCRT). A total of 18 outpatients with NPC administered oral nutritional supplementation intervention at home during the course of CCRT were designated as the HEN group, whereas 36 patients with NPC who had previously completed CCRT were retrospectively included as the control group. Patient Generated Subjective Global Assessment, body mass index (BMI), and blood test were evaluated prior to CCRT. During the course of CCRT, blood test was assessed every 2 weeks. In male patients, hemoglobin (HB) and red blood cell were decreased (P < .05) in both HEN and control group after CCRT, whereas white blood cell (WBC) started to decrease since week 2 of CCRT in the control group but maintained in the HEN group which was significantly higher than the control (5.05 ± 1.29 vs 3.77 ± 1.5, P < .05). In female patients, HB and WBC were reduced in control group during CCRT, whereas these indicators also maintained in the HEN group. Surprisingly, all patients with lower BMI (<24 kg/m2 ) had a significant increase in platelet (PLT) after CCRT (200.78 ± 58.03 vs 253.00 ± 69.82, P < .05), while had steady HB and WBC values in the HEN group. At the end of CCRT, WBC and PLT of the HEN group were both higher than those in the control group (5.21 ± 1.07 vs 3.37 ± 1.52), (253.00 ± 69.82 vs 165.57 ± 59.56) (P < .05 for both). Our findings suggest that HEN is effective in preventing myelosuppression during CCRT for patients with NPC. Our findings suggest that HEN is effective in preventing myelosuppression during CCRT for patients with NPC.

Arginine, glutamine, and fish oil supplementation in cancer patients treated with concurrent chemoradiotherapy: A randomized control study

We evaluated the effectiveness of arginine, glutamine, and fish oil supplementation in patients’ ability to adhere to the planned regimen and associated toxicities in patients who received concurrent chemoradiotherapy (CCRT). Eighty-eight cancer patients were randomized into 2 groups, A; regular diet and B; regular diet plus nutritional supplementation during their CCRT course. Logistic regression was used to assess the association between toxicity and the study groups. Survival analysis was performed using the Kaplan-Meier method, and log-rank tests were used to compare between the 2 groups. Among 88 patients, 45%, 32%, and 23% were head and neck cancer, esophageal cancer, and cervical cancer patients, respectively. Significantly higher grade 3-4 hematologic toxicities were found in group A than in group B (23% vs 5%, P= 0.03). The CCRT completion rate was lower in group A than in group B (75% vs 91%), but the difference was not statistically significant (P= 0.09). Adjusted for type of cancer and age, group B patients were associated with lower hematologic toxicities of CCRT, P= 0.03. Two-year overall survival was 47% for group A, and 61% for group B, P= 0.22. In conclusion, incidence of severe hematologic toxicities were significantly lower in patients with arginine, glutamine, and fish oil supplementation during CCRT. These findings, therefore, need further studies on the isocaloric design.

Prognostic value of delta inflammatory biomarker-based nomograms in patients with inoperable locally advanced NSCLC

ObjectiveInflammation plays critical roles in tumor growth and progression, and can be adversely affected by chemotherapy and radiotherapy. However, there have been few studies on the prognostic value of delta (Δ) inflammatory biomarkers before and after chemoradiotherapy in patients with locally advanced non-small cell lung cancer (LA-NSCLC). MethodsIn this study, pre/post-treatment and Δ inflammatory biomarkers of 370 patients who were diagnosed as having inoperable LA-NSCLC in Shandong Cancer Hospital between January 2005 and January 2016 were analyzed. Nomograms were then established for predicting prognosis. ResultsMedian overall survival (OS) and progression free survival (PFS) for all patients were 28.1 (range 1.9–129.0) months and 11.1 (range 1.7–58.7) months, respectively. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) significantly increased and the lymphocyte-to-monocyte ratio (LMR) significantly decreased during the concurrent chemoradiotherapy course (P < 0.001, P < 0.001, and P < 0.001, respectively). Multivariate analysis revealed that pre-LMR, ΔNLR, and minimum absolute lymphocyte counts were independent predictors of OS (P = 0.027, P = 0.012, and P = 0.015, respectively) and post-LMR, post-NLR, and ΔNLR were independent predictors of PFS (P = 0.014, P = 0.001, and P = 0.036, respectively). Nomograms for OS and PFS were established by combining all significant inflammatory markers and clinicopathological characteristics. The concordance indexes for OS and PFS were 0.709 and 0.688, respectively. ConclusionPost-treatment and Δ inflammatory biomarkers may have more prognostic significance than baseline measurements of inflammatory biomarkers in LA-NSCLC patients. The proposed nomograms based on the dynamic inflammatory biomarkers and clinicopathological factors may be practical and widely available for evaluating the prognosis of patients with inoperable LA-NSCLC.

Assessment of fatigability, depression, and self-esteem among head-and-neck carcinoma patients in a tertiary care hospital in South India.

Head and Neck Carcinoma (HNCs) are the most common form of cancer in India. Patients with head-and-neck carcinomas often suffer from various distressing symptoms. The exact cause of these symptoms, as to whether disease or treatment or other factor induced, needs to be established. This study was done to assess fatigability, depression, and self-esteem among HNC study group before start, during, and in postradiation period and to find out the determinants of these parameters. Seventy newly diagnosed HNC patients and equivalent number of age- and gender-matched controls were interviewed using standardized questionnaires, before start of concurrent chemoradiotherapy (CCRT). The study group patients were interviewed again in the 4th week and postcompletion of CCRT in the 7th week. Mean age of the study group was 55.1 ± 11.3 years. Three-fourth of them (52 [74.3%]) were males. Majority of them (26 [37.1%]) had oral carcinomas. Baseline fatigue (P < 0.001) and depression scores (P < 0.001) were significantly more, while self-esteem scores (P = 0.004) were significantly less among the study group compared to controls before the onset of radiation. Mean fatigue and depression scores were found to significantly increase (P < 0.001), while self-esteem scores were found to significantly deteriorate (P < 0.001) over the course of CCRT among these patients. There was significant positive correlation (P < 0.001) between fatigue and depression scores and negative correlation (P < 0.001) of these parameters with self-esteem scores before, during, and after CCRT. There was no association between age and gender of the study group with any of these parameters. Multivariate analysis showed that baseline fatigue was significant (P < 0.001) and, depression after completion of the entire course of CCRT was significantly influenced by baseline depression levels (P = 0.011). Fatigue and depression need to be periodically screened among HNC study group on CCRT so as to initiate prompt remedial measures for its alleviation.

Comparison and Assessment of Head and Neck Squamous Carcinoma in Younger and Older Patients Treated with Chemo Radiotherapy

Introduction: Head and neck cancer (HNC) is the 6th most common cancer globally. Unfortunately, even though more than 25% of cancers are diagnosed in people over 60 years, they are often less extensively investigated and undertreated than younger patient and seldom included in clinical trials. The study aimed to compare the profile of younger and elderly patients in terms of compliance, toxicities, and clinical outcomes in head and neck cancers treated with chemo-radiotherapy. Materials and Methods: Fifty patients were included in the study and patients were distributed in two groups, age ≤ 60 years of age and &gt;60 years of age, and were planned to deliver standard radiotherapy at a dose of 70 Gy in 35 fractions over 7 weeks with concurrent chemotherapy dose Cisplatin 35 mg/ m2 weekly followed by compliance assessment from 3 months of follow up to at least up to 6 months. Result: In the present study, it was observed that radiotherapy compliance was similar in the elderly group as in younger group. Our study also observed that though chemotherapy compliance in terms of number of the cycle was lower in elderly patients than younger patients due to increase hematological toxicities, they were of grade I/II toxicity. No significant difference in severe Grade III/IV toxicity was observed in elderly group in comparison to the younger group. Conclusion: The present study suggests that elderly patients should get a complete radical course of concurrent chemo radiotherapy as in younger patients with good supportive care to overcome treatment-related toxicities.

Preliminary Results of Definitive Concurrent Chemoradiation Therapy With S-1 and Nedaplatin for Locally Advanced Esophageal Squamous Cell Carcinoma

This trial aimed to evaluate the efficiency and safety of S-1 and nedaplatin combined with definitive concurrent radiotherapy in locally advanced esophageal squamous cell carcinoma patients. We collected retrospectively the data of definitive CRT with nedaplatin and S-1.All of patients were pathologically proved locally advanced esophageal squamous cell carcinoma (T3-4N0M0 or anyTN+M0) in this study. patients received IMRT with a simultaneous integrated boost (SIB-IMRT) to primary tumor and involved lymph nodes(60.2Gy and 50.4Gy in 28 fractions).Nedaplatin 70 mg/m2 was given on days 1 and 22, and concurrent S-1 was administered twice daily at a dosage (50mg/m2/d) on days 1-14,every 3 weeks. Patients received two courses of concurrent chemoradiotherapy with or without two additional courses as adjuvant therapy every 4 weeks. From July 2013 to December 2015, 47 patients were included (27 with stage II, 20 with stage III, AJCC 7th). The median age was 61 years (range: 43-74 years), thirty-one (66 %) patients completed the prescribed full dose and concurrent two cycles. A complete response was achieved in 32 patients (68 %).With a median follow-up of 17 months (range 8-35), the actually 1-year overall survival (OS), locoregional recurrence free survival (LRFS) and distant-metastasis free survival (DMFS) in this study were 97.3%, 81.6% and 92.9%, respectively. Grade ≥3 leukopenia°×°û, thrombocytopeniaѪÐ″å, and anemiaƶѪ occurred in 8%, 14%, and 4 % of the patients, respectively.. The most common nonhematologic toxicity was esophagitis including 8 patients with grades. No patients experienced Grade 5 adverse events within the 30 days after chemoradiotherapy. S-1 plus Nedaplatin with concurrent IMRT was feasible and efficacious for locally advanced esophageal cancer patients. Toxicities were tolerable and clinically manageable. More prospective studies are warranted to clarify this issue.

Exploring the Usefulness of Concurrent Chemoradiation for Bulky Disease in the Setting of Advanced/Inoperable or Metastatic Breast Cancer

Improvements in systemic therapy (ST) have improved survival for breast cancer (BC) patients with locally advanced/inoperable and metastatic disease. Therefore, traditional palliative radiotherapy courses (e.g. 30 Gy/10 fractions) may not be sufficient treatment to secure durable control of bulky locoregional or symptomatic metastases and more aggressive approaches may be warranted. We sought to characterize the outcome of treating this population with concurrent chemoradiotherapy (CRT). We queried our institution's pharmacy database for BC patients treated with capecitabine (C) from 2012-2016 to identity patients that received CRT. Demographic, disease characteristics, treatment information and outcome was collected. Local failures (LF) were classified as progression documented within the irradiated field. All other failures were classified as distant failures (DF). Competing risks analysis was performed to estimate LF/DF. We used the linear quadratic formalism to calculate the biologically effective dose of the different RT regimens assuming α/β=3 (BED3). We chose to assess differences in LF using a cutoff value BED=80 Gy3 (equivalent to common whole breast RT regimens). Of 323 patients in the C database, 33 patients underwent 35 courses of CRT. 48% were ER+/PR+, 45% triple-negative, and 18% HER2+. For CRT, C (500 mg-1500 mg PO BID, was most commonly used (N=26); 7 patients received Carboplatin (AUC=2 IV weekly) or Cisplatinum (22.5-30 mg/m2 IV weekly); 1 patient received doxorubicin-liposomal 32mg/m2 IV q3 weeks; 1 patient received gemcitabine 300mg/m2 IV weekly. At the time of CRT, 4 pts had inoperable disease, 11 pts had local-regional recurrence (LRR), and 18 patients had distant metastatic disease (DM). The median number of prior lines of ST was 4 (range, 1-11) for DM patients and 1 (1-4) for inoperable/LRR patients. Median PTV was 886 cc (range, 180-2956 cc) for inoperable/LRR and 427 cc (34-3336 cc) for DM. 28% were treated with ≤2Gy/fraction to a median dose of 60 Gy (range, 36-66 Gy); 46% were treated at 2.5-3Gy/fraction to a median dose of 45 Gy (30-60 Gy); and 26% were treated at >3Gy/fraction to a median dose of 48 Gy (22.8-68 Gy). Median follow-up was 8 months. The 1-year LF was 23%, DF 71%, and OS rate 54%. Patients that received BED3≥80 Gy vs. <80 Gy had numerically lower rates of LF at 1 year (18% vs. 39%, p=0.09). Grade 3 acute toxicity was low (9% Grade dermatitis; 9% hematologic). Patients resumed standard dose ST at a median of 10.5 days after completion of CRT. We found that CRT for bulky disease in the breast, nodal or metastatic sites is well-tolerated in heavily pre-treated BC patients. Patients returned promptly to ST and at 1 year an overall local control of 77% was achieved, and 82% when an RT regimen with BED>80 Gy3 was used. The predominant failure pattern was at distant sites outside the RT field. We suggest that this approach warrants future prospective studies and hypofractionated regimens with a BED>80 Gy3 is recommended.

Tumor compactness improves the preoperative volumetry-based prediction of the pathological complete response of rectal cancer after preoperative concurrent chemoradiotherapy.

In addition to clinical factors (tumor and node stage) and treatment factors (equivalent radiotherapy dose and chemotherapy regimen), we assessed whether different performances of various tumor volume measurements help predict the pathological complete response (pCR) of locally advanced rectal cancer (LARC) after preoperative concurrent chemoradiotherapy (CCRT). A total of 122 patients with LARC treated with a long course of CCRT, between December 2009 and March 2015, were enrolled in this bi-institutional study. Tumor delineation was based on standard T2-weighted magnetic resonance imaging or contrast-enhanced computed tomography before CCRT. Tumor compactness was defined as the ratio of the volume and the surface area. The tumor compactness-corrected TV (TCTV) was defined as the ratio of the real TV (RTV) and tumor compactness. Twenty-three (18.9%) patients had a pCR. Areas under the curve of the receiver operating characteristic for pCR prediction calculated using the RTV, cylindrical approximated TV (CATV), and TCTV were 0.724, 0.747, and 0.780, respectively. The prediction performance of TCTV was significantly more efficient than that of both RTV (P = 0.0057) and CATV (P = 0.0329). Multivariate logistic regression analysis revealed tumor compactness (P = 0.001), RTV (P = 0.042), and preoperative clinical nodal status (P = 0.044) as significant predictors of a pCR. In addition, poor tumor compactness was closely associated with lymphovascular space invasion (P = 0.008) and pathological nodal status (P = 0.003). For patients with LARC receiving preoperative CCRT, tumor compactness is a useful radiomic parameter for improving the volumetric based prediction model.