Nutri-PEITC Jelly Significantly Improves Progression-Free Survival and Quality of Life in Patients with Advanced Oral and Oropharyngeal Cancer: A Blinded Randomized Placebo-Controlled Trial.

TP53 mutation is associated with cancer progression. Novel strategies to reboot p53 are required to stabilize the disease and improve survival. This randomized placebo-controlled trial investigated safety and efficacy of Nutri-PEITC Jelly (a texture-modified nutritious diet fortified with ß-phenethyl isothiocyanate (PEITC) on oral cancer. Seventy-two patients with advanced-staged oral or oropharyngeal cancer were randomly assigned to study and control groups, who consumed 200 g of Nutri-Jelly with and without 20 mg of PEITC, respectively, 5 days/week for 12 weeks. Outcomes, including adverse events, health-related quality of life (HRQOL), progression-free survival (PFS), tumor response, serum p53, and cytochrome c, were measured at 0, 1, and 3 months. Results show that the study group had a higher proportion of participants with improved HRQOL, stable disease, and increased serum p53 levels than those in the control group (p < 0.001). The PFS time in the study group was significantly longer than that of the control group (p < 0.05). Serum cytochrome c levels were non-significantly decreased in the study group. No serious intervention-related adverse events occurred in either group. In conclusion, Nutri-PEITC Jelly intake for 3 months is safe, stabilizes the disease, improves quality of life and progression-free survival, and might re-activate p53 in advanced-stage oral and oropharyngeal cancer patients.

High-dose Intensity-modulated proton therapy versus Standard-dose Intensity-modulated RadIation therapy for esophageal squamous cell carcinoma (HI-SIRI): study protocol for a randomized controlled clinical trial.

BACKGROUND: Chemoradiotherapy is the standard of care for esophageal cancer as a neoadjuvant treatment before surgery, or as a definitive treatment for unresectable disease. Intensity-modulated radiotherapy (IMRT) has been considered the standard radiation technique. However, patients suffer from treatment-related toxicities, and most die from disease progression or recurrence. With emerging technological advancement, proton therapy has theoretical advantages over IMRT because it offers apparent dosimetric benefits to allow dose escalation to the target while better sparing surrounding tissues such as the lungs, heart, liver, and spinal cord. The purpose of this study protocol is to investigate the survival benefit of proton therapy using modern intensity-modulated proton therapy (IMPT) compared to standard IMRT for esophageal cancer. METHODS: This is a two-arm open phase II/III multi-institution randomized controlled trial. Eligible patients will have histologically confirmed squamous cell carcinoma of the thoracic esophagus with no evidence of tracheoesophageal/esophagobronchial fistula or distant metastasis. After stratification according to resectability status (resectable vs. borderline resectable/unresectable), a total of 232 patients will be randomized to receive IMPT or IMRT using a 1:1 allocation ratio. In resectable cases, surgical resection following concurrent chemoradiation will be attempted for the patients who are medically fit at the time of surgery. In those with initially borderline resectable/unresectable disease, definitive concurrent chemoradiation will be performed. The phase II study will assess safety (toxicity and postoperative complications) and feasibility (recruitment rate and chemoradiation dose modification) in 40 patients into each arm. The study will then continue into phase III, further recruit 76 patients into each arm, and compare progression-free survival between IMPT vs IMRT groups. The secondary endpoints will be overall survival, local and distant control, toxicities, health-related quality of life, and cost-utility. This protocol describes a detailed radiotherapy and chemotherapy. DISCUSSION: This randomized clinical trial will demonstrate the clinical benefit of IMPT in esophageal cancer treatment in terms of survival and toxicity outcomes which will further establish high-level evidence for radiation modality in squamous cell carcinoma of the thoracic esophagus. TRIAL REGISTRATION: TCTR20200310006 . Registered 10 March 2020.

Salvage Treatment and Outcomes of Locally Advanced Cervical Cancer after Failed Concurrent Chemoradiation with or without Adjuvant Chemotherapy: Post Hoc Data Analysis from the ACTLACC Trial.

OBJECTIVES: To evaluate the type of salvage treatment and outcomes of patients with locally advanced cervical cancer who failed treatment with concurrent chemoradiation with or without adjuvant chemotherapy. METHODS: This was post hoc analyses of data from the randomized trial which included 259 patients who had FIGO stage IIB-IVA and had either pelvic radiation therapy concurrent with cisplatin followed by observation or paclitaxel plus carboplatin. Data of the patients who failed primary treatment were collected: type of salvage treatments, time to progress after salvage therapy, progression-free (PFS) and overall survivals (OS). RESULTS: After primary treatment, 85 patients had either persistence (36.5%), progression (18.8%), or recurrences (44.7%). The sites of failure were loco/regional in 52.9%, systemic failure in 30.6%, and loco-regional and systemic in 16.5%. Chemotherapy was given in 51.8%, being the sole therapy in 34.1%. Majority were combination agents (31.8%), with paclitaxel/carboplatin as the most common regimen. Radiation to the metastatic sites along with chemotherapy was used in 14.1% whereas palliative radiation therapy or supportive care was used in approximately 10% of each. The median time from the start of salvage treatment to progression was 9.2 months (range 0.2-64.0 months) with median PFS of 11.2 months (95% CI, 7.2-15.3 months). Median overall survival 27.3 months (95% CI, 4.4-69.6 months). CONCLUSIONS: Chemotherapy, either alone or with radiation therapy, was the most common salvage treatment in LACC after failure from primary treatment. The time to progress and PFS were less than 1 year with OS of approximately 2 years.

Long-Term Outcomes and Sites of Failure in Locally Advanced, Cervical Cancer Patients Treated by Concurrent Chemoradiation with or without Adjuvant Chemotherapy: ACTLACC Trial.

OBJECTIVES: To evaluate sites of failure and long-term survival outcomes of locally advanced stage cervical cancer patients who had standard concurrent chemo-radiation (CCRT) versus those along with adjuvant chemotherapy (ACT) after CCRT. METHODS: Patients aged 18-70 years who had FIGO stage IIB-IVA without para-aortic lymph node enlargement (excluding by International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IIIC2r), The Eastern Cooperative Oncology Group (ECOG) scores 0-2, and non-aggressive histopathology were randomized to have CCRT with weekly cisplatin followed by observation (arm A) or ACT with paclitaxel plus carboplatin every 4 weeks for 3 cycles (arm B). RESULTS: From 2015-2017, 259 patients were evaluated. The majority of patients were in stage II and had squamous cell carcinoma with a median tumor size of 5 cm. After the median follow-up of 40.87 months, 17.1% of the patients in arm A and 12.3% of the patients in arm B experienced recurrences (p=0.280). Adding all events of failure (persistence/progression/recurrence), treatment failures tended to be lower in arm A than in arm B: 13.2 versus 21.5 % for loco-regional failure (p = 0.076) and 3.9 versus 6.9% for loco-regional failure and systemic failure (p = 0.278). On the other hand, systemic failure tended to be higher in arm A than in arm B: 13.2% versus 6.9% (p =0.094). The 5-year progression-free survival and 5-year overall survival of patients in both arms were not significantly different. CONCLUSIONS: ACT with paclitaxel plus carboplatin after CCRT did not improve response or survival of patients compared to CCRT alone. Although systemic failure tended to be lower in patients who had ACT after CCRT than those who had only CCRT, loco-regional failure with or without systemic failure tended to be higher. However, all of these differences were not statistically significant.

Cost-utility analysis of adjuvant chemotherapy after concurrent chemoradiation in patients with locally advanced cervical cancer.

INTRODUCTION: This study aimed to compare the cost utility of concurrent chemoradiation (CCRT) to CCRT followed by adjuvant chemotherapy (CCRT/ACT) in locally advanced cervical cancer (LACC) using provider and societal viewpoints. METHODS: Data from our trial which was a multi-centre study evaluating the efficacy of ACT compared to CCRT/ACT were entered into a decision tree model. The data included clinical probability, direct medical and non-medical costs, and utility obtained from the patients. The total cost, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICER) were estimated for a time horizon of 3 years. All costs and outcomes were discounted at 3% annually. RESULTS: The cost of CCRT and CCRT/ACT was approximately 3,058 and 6,896 USD and 4,309 and 7,480 USD from provider and from societal viewpoints, respectively. The QALYs for CCRT and CCRT/ACT were 2.31480 and 2.32045, respectively. The ICER was 569,575 USD per QALY. For stage III-IVA LACC, the ICER was 28,050 USD per QALY. In the sensitivity analysis, the cost of ACT was the most significant influential parameter on the ICER. The ICER would be 0.26-fold lower if the cost of ACT was reduced by 25%. At the current ceiling threshold of 5,000 USD/QALY, CCRT had a 100% probability of being the best option. CONCLUSIONS: In the Thai context, CCRT is more cost effective than CCRT/ACT for stage IIB-IVA LACC. CCRT/ACT may be considered only for stage III-IVA LACC because it has a lower ICER than other types of LACC.

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.

Randomized comparison of fluorouracil plus cisplatin vs. cisplatin as an adjunct to radiation therapy in stage IIB-IVA squamous cell carcinoma of the cervix: pilot study.

OBJECTIVE: To compare the efficacy and toxicity of pelvic radiotherapy with concomitant cisplatin plus fluorouracil versus cisplatin alone in patients with locally advanced squamous cell cervical cancer. MATERIAL AND METHOD: Twenty women with squamous cell cervical cancer were randomly assigned to receive ether standard whole pelvic radiotherapy with concurrent cisplatin and fluorouracil infusion every 4 weeks or the same radiotherapy with concurrent cisplatin every 1 week. The primary endpoint was the response rate. RESULTS: All patients in cisplatin plus fluorouracil regimen and in cisplatin regimen had complete response. In cisplatin group there was higher frequencies of adverse hematologic effects. Grade 3 or 4 neutropenia occurred in 10% of the cisplatin plus fluorouracil group and in 40% of the cisplatin group (p = 0.049). CONCLUSION: No difference was found in the response rate, but higher frequencies of hemotological adverse effects in the cisplatin group.

Reducing radiation dose to pelvic small bowel in cervical cancer patients treated with Ir-192 intracavitary brachytherapy by using urinary bladder distension.

OBJECTIVES: Several techniques and devices have been used in an attempt to minimize radiation dose to gastrointestinal tract while giving pelvic radiation. We evaluated the effect of urinary bladder distension to displace pelvic small bowel out of intracavitary brachytherapy field to minimize radiation dose to small bowel in cervical cancer patients. MATERIAL AND METHOD: Eleven cervical cancer patients who received Ir-192 intracavitary brachytherapy with tandem and transverse ovoids were included in this study. Oral contrast material was used to visualize pelvic small bowel. Urinary bladder was distended by injection 125-200 ml. normal saline solution. Pelvic radiograph, anteroposterior and lateral view, was performed before and after bladder distention for brachytherapy treatment planning and comparing radiation dose at small bowel. RESULTS: The average maximum radiation dose at small bowel before and after bladder distension were 3123 cGy and 1998 cGy respectively. The summation of small bowel dose was reduced 54.17% (p = 0.002). CONCLUSION: Urinary bladder distension could effectively displace pelvic small bowel and reduce the radiation dose to small bowel from Ir-192 intracavitary brachytherapy in cervical cancer patients.