Pretreatment Esophageal Wall Thickness Associated with Response to Chemoradiotherapy in Locally Advanced Esophageal Cancer.

PURPOSE: A multimodality approach using concurrent chemoradiotherapy (CRT) followed by esophagectomy has been the standard treatment in patients with locally advanced esophageal squamous cell carcinoma (ESCC). Computed tomography (CT) is widely utilized to evaluate esophageal cancer before and after CRT. This study evaluated the utility of pretreatment maximal esophageal wall thickness on CT scans to predict treatment outcomes after CRT in patients with locally advanced ESCC. METHODS: Eighty-one patients with T3 locally advanced ESCC, whom were treated completely with CRT with and without surgery, and had available CT scans before and after CRT at a university hospital between 2005 and 2015, were retrospectively reviewed. RESULT: Twenty patients (24.7%) had esophagectomy after neoadjuvant CRT and sixty-one patients (75.3%) had definitive CRT. The maximal esophageal wall thicknesses were measured retrospectively and correlated with the response and survival after treatment. A total of 40% of neoadjuvant CRT patients achieved a pCR. There was a significant difference in pretreatment maximal esophageal wall thickness between the pCR and non-pCR groups (mean 11.9 ± 5.3 mm versus 16.9 ± 3 mm; p = 0.01). Pretreatment maximal esophageal wall thickness < 10 mm was significantly related to better overall survival than ≥ 10 mm (median survival 79 months versus 15 months; HR 3.21, 95%CI 1.14-9; p = 0.02). The neoadjuvant CRT group had significantly better survival than the definitive CRT group (median survival 51 months versus 14.5 months; HR 0.46; 95%CI 0.25-0.85; p = 0.01). CONCLUSION: In our study, pretreatment esophageal wall thickness of T3 locally advanced ESCC is a useful indicator for predicting survival and pCR after treatment.

A randomized controlled trial comparing concurrent chemoradiation versus concurrent chemoradiation followed by adjuvant chemotherapy in locally advanced cervical cancer patients: ACTLACC trial.

OBJECTIVE: To compare response rate and survivals of locally advanced stage cervical cancer patients who had standard concurrent chemoradiation therapy (CCRT) alone to those who had adjuvant chemotherapy (ACT) after CCRT. METHODS: Patients aged 18-70 years who had International Federation of Gynecology and Obstetrics stage IIB-IVA without para-aortic lymph node enlargement, Eastern Cooperative Oncology Group scores 0-2, and non-aggressive histopathology were randomized to have CCRT with weekly cisplatin followed by observation (arm A) or by ACT with paclitaxel plus carboplatin every 4 weeks for 3 cycles (arm B). RESULTS: Data analysis of 259 patients showed no significant difference in complete responses at 4 months after treatment between arm A (n=129) and arm B (n=130): 94.1% vs. 87.0% (p=0.154) respectively. With the median follow-up of 27.4 months, 15.5% of patients in arm A and 10.8% in arm B experienced recurrences (p=0.123). There were no significant differences of overall or loco-regional failure. However, systemic recurrences were significantly lower in arm B than arm A: 5.4% vs. 10.1% (p=0.029). The 3-year progression-free survival (PFS) and 3-year overall survival (OS) of the patients in both arms were not significantly different. The hazard ratio of PFS and OS of arm B compared to arm A were 1.26 (95% CI=0.82-1.96; p=0.293) and 1.42 (95% CI=0.81-2.49; p=0.221) respectively. CONCLUSIONS: ACT with paclitaxel plus carboplatin after CCRT did not improve response rate and survival compared to CCRT alone. Only significant decrease of systemic recurrences with ACT was observed, but not overall or loco-regional failure. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02036164, Thai Clinical Trials Registry Identifier: TCTR 20140106001.

Effects of zinc sulfate supplementation on cell-mediated immune response in head and neck cancer patients treated with radiation therapy.

Zinc deficiency is an important factor that impairs cellular immunity and contributes to low T lymphocyte counts in head and neck cancers. Persistent T lymphopenia is clinically relevant in terms of tumor persistence and/or recurrence. The primary objective was to evaluate the impact of zinc sulfate supplementation on the absolute numbers of circulating T lymphocytes and T lymphocyte subpopulations. The secondary objectives were to evaluate overall survival, progression-free survival, and the adverse events of zinc sulfate. Seventy-two head and neck cancer patients were enrolled in a randomized, double-blind, placebo-controlled trial. Zinc sulfate 50 mg in 10 cc and an identically appearing placebo were self-administered 3 times daily at meal times. Blood samples were obtained for complete blood count, total T lymphocytes and T lymphocyte subpopulations before radiation therapy as baselines, at the fifth week during radiation therapy, and at the first month after completion of radiation therapy. The baseline characteristics of patients, tumors, and treatments and the baseline lymphocyte parameters were not significantly different between the 2 groups. Zinc sulfate supplementation during head and neck radiation therapy showed no increase in absolute numbers of circulating T lymphocytes, T lymphocyte subpopulations, or survival with acceptable side effects.

Randomized study of antiinflammatory and immune-modulatory effects of enteral immunonutrition during concurrent chemoradiotherapy for esophageal cancer.

Concurrent chemoradiotherapy (CCRT) induces toxicities from inflammation and immunological suppression. Omega-3 fatty acids, glutamine, and arginine are therapeutic factors that can attenuate such inflammation and promote cellular immunity. The question is whether immunonutrition (IN) during CCRT reduces inflammation and improves the immune function in patients with esophageal squamous cell carcinoma (ESCC). Seventy-one locally advanced ESCC patients being treated with CCRT (5-FU and cisplatin) were randomized into 2 groups. The IN group received a combination of omega-3 fatty acids, glutamine, and arginine, whereas the control group received standard formula. The levels of C-reactive protein (CRP), tumor necrosis factor (TNF), interferon-gamma (IFN), interleukin (IL-6, IL-10), CD3, CD4, CD8, white blood cells, neutrophils, and total lymphocytes were measured before and during treatment. The levels of CRP (P = 0.001) and TNF (P = 0.014) increased more during treatment in the control group than the treatment group, whereas IFN, IL-6, and IL-10 were similar but not significantly. CD3, CD4, CD8, white blood cells, neutrophils, and total lymphocytes decreased more in the control group than in the treatment group, but not significantly. Enteral IN during CCRT reduced the increase of inflammatory cytokine levels.

A randomized double-blind, placebo-controlled trial of zinc sulfate supplementation for alleviation of radiation-induced oral mucositis and pharyngitis in head and neck cancer patients.

OBJECTIVE: To determine the efficacy of zinc sulfate supplementation in reducing ofradiation-induced oral mucositis and pharyngitis in head and neck cancer patients. MATERIAL AND METHOD: One hundred forty four head and neck patients were enrolled in a randomized, double-blind, placebo-controlled trial. Patients who received radiation therapy alone or postoperative radiation therapy were eligible. Radiation therapy used conventional fractionation with 1.8 to 2.0 Gy perfraction, to total doses of 50 to 70 Gy over five to seven weeks. Drug and identically appearing placebo were self-administered 50 mg (10 cc) per meal, three times a day at mealtime. The zinc sulfate and placebo were administered beginning on the first day of radiation, and continued daily including weekends until radiation was completed Patients were evaluated before radiation, weekly during radiation and at the first month after completion of radiation. RESULTS: The baseline characteristics of patients, tumor, and treatment were not significantly different between the two groups. There were no statistically significant differences between the two treatment groups in frequency of patients experiencing greater than or equal to grade 2 oral mucositis andpharyngitis at each week during radiation and at the first month after completion of radiation. Six patients (17%) in the zinc sulfate and ten patients (23%) in placebo group developed grade 3 oral mucositis, which was not significantly different. Twenty-two patients (32%) in the zinc sulfate and nineteen patients (27%) in the placebo group developed grade 3 pharyngitis, which was not signifiibantly different. However there was no observation of grade 4 oral mucositis and pharyngitis in either group. Nausea and vomiting were mostly of mild degree. Adverse events were not statistically significant different between the two groups. CONCLUSION: It was concluded that zinc sulfate administered during head and neck radiation therapy produced no significant benefit in relieving radiation-induced oral mucositis and pharyngitis with acceptable side effects.

Concurrent chemoradiotherapy with carboplatin followed by carboplatin and 5-fluorouracil in locally advanced nasopharyngeal carcinoma.

BACKGROUND: This study aimed to evaluate acute major toxicities, the response rate, 3-year overall survival and progression-free survival rate of locally advanced nasopharyngeal carcinoma patients on concurrent carboplatin chemoradiotherapy followed by carboplatin and 5-fluorouracil. METHODS: A prospective study of fifty patients diagnosed with locally advanced nasopharyngeal carcinoma received conventional radiation therapy with a total dose of 6600-7000 cGy in 6-7 weeks and concurrent chemotherapy of three cycles of carboplatin during radiotherapy, followed by adjuvant chemotherapy using carboplatin plus 5-fluorouracil for two cycles. RESULTS: Weight loss and mucositis were the two most common acute major grades 3-4 toxicities (42%). Myelosuppression occurred subsequently, including leukopenia (30%), neutropenia (20%), anemia (12%), and thrombocytopenia (6%). Only 8% of patients developed grades 3-4 nausea and vomiting. No patients had renal and electrolyte abnormalities. Regarding the response evaluation, 100% of patients achieved an objective response rate of the primary tumor (92% complete response, and 8% partial response). Similarly, all patients also achieved an objective response rate of the neck node (64% complete response and 36% partial response). The 3-year overall survival rate and progression-free survival rate were 89.7% and 72.7%, respectively. CONCLUSIONS: Concurrent chemoradiotherapy with carboplatin followed by carboplatin and 5- fluorouracil could be considered as an alternative regimen for locally advanced nasopharyngeal carcinoma patients pertaining to a good overall response rate, 3-year overall survival and progression-free survival rate with good tolerability.