Role of adjuvant therapy in resected periampullary adenocarcinoma: A propensity matched case-control study.

Backgrounds/Aims: The published data had contradictory information on the role of adjuvant therapy on resected periampullary carcinomas (PACA). The study was performed to evaluate the survival benefit of adjuvant treatment. Methods: This was a propensity score matched case-control study from a prospectively maintained database from 2004-2019. The study included patients with nonpancreatic PACA who underwent curative resection. The patients (cases) who received adjuvant chemotherapy were compared with patients (controls) who were observed alone after surgery. Results: Of 510 patients with PACA, 230 patients (cases = 107, controls = 123) formed the unmatched study cohort. After propensity score matching, 140 patients (cases = 70, controls = 70) formed the matched study cohort. The median overall survival (OS) was similar in cases than controls in the unmatched population but doubled non-significantly in cases after matching (unmatched population, 54 months vs. 54 months, p-value = 0.624; matched population, 71 months vs. 36 months, p-value = 0.087). However, the median recurrence-free survival (RFS) was non significantly higher in the control group (unmatched population, 59 months vs. 38 months, p-value = 0.195; matched population, 53 months vs. 40 months, p-value = 0.797). In cox regression analysis, age < 60 years, advanced T stage, and presence of perineural invasion were independent factors for worse RFS, while tumor recurrence was an independent factor for poor OS. Conclusions: Patients with nonpancreatic PACA may have an OS benefit from adjuvant chemotherapy, and this needs to be validated with large prospective randomized studies.

Prospective Randomized Controlled Trial Comparing Adjuvant Chemotherapy vs. No Chemotherapy for Patients with Carcinoma of Gallbladder Undergoing Curative Resection.

BACKGROUND: Gallbladder carcinoma (GBC) has a dismal prognosis even after curative resection. The objective of the study was to evaluate the effect of adjuvant chemotherapy in patients with GBC undergoing curative resection in a randomized control trial (RCT). METHODS: A single-center open-labeled prospective RCT was done from January 2012 to June 2018. R0 curative resected GBC patients were randomized in 1:1 to either surveillance alone (control group) or adjuvant chemotherapy (gemcitabine and cisplatin (GemCis group)) for 6 cycles. The primary outcome was disease-free survival (DFS), and the secondary outcomes were overall survival (OS) and toxicity profile. RESULTS: On the evaluation of 362 patients with GBC, 50 patients were enrolled in each control or GemCis group. Per protocol (PP), it comprised 96 patients. The demographic and clinical profile was similar between the two groups except in the lower nodal stage where patients were higher in the control group (p = 0.01). Recurrences were similar between groups (control 44% vs GemCis 56%; p = 0.23). On the intention to treat (ITT), analyses of median DFS (not reached vs. 24 months, p = 0.14) and OS (not reached vs. 31 months, p = 0.10) were similar between groups. On PP, analyses of median DFS (not reached vs. 24 months, p = 0.16) and OS (not reached vs. 31 months, p = 0.09) were similar between groups. The common toxicity profile was hematological followed by gastrointestinal symptoms. CONCLUSIONS: Adjuvant GemCis therapy for 6 cycles does not improve DFS or OS than R0 surgery alone patients with GBC. TRIAL REGISTRATION: NCT02778308 ( https://www.clinicaltrials.gov ).

"Christie Regimen" palliative radiotherapy in advanced head-and-neck cancer: A single-center experience.

BACKGROUND: Relevance of aggressive treatment in advanced head neck squamous cell cancers(HNSCC) is debatable in view of expected poor outcome. Long treatment duration only adds up to the cost of treatment without any improvements in outcomes. AIMS AND OBJECTIVES: To assess the outcomes of hypofractionated "Christie" palliative radiotherapy regimen in advanced HNSCC. MATERIALS AND METHODS: Patients of advanced HNSCC registered from June 2015 to June 2019 were treated by parallel pair field technique on Cobalt60 machine (Theatron 780E) to total dose of 50 Gray/16 fractions over 3.2 weeks. Toxicity was scored using Radiation Therapy Oncology Group (RTOG) criteria and response was evaluated as per WHO criteria. RESULTS: Records of 110 patients of HNSCC with mean age of 56.19 years were analysed. Evaluation at 4-8 weeks after radiotherapy resulted in a complete response (CR) in 19.1%, partial response (PR) in 32.7%, stable disease (SD) in 29.1% and progressive disease (PD) in 3.6%, while 15.5% patients did not report for post treatment evaluation. Median progression free survival was 9.52 months (95% CI 5.9 - 13.1 months). The median overall survival was 12.7 ± 2.2 months (95% CI 8.2 - 17.2). Median time to progression after completion of radiotherapy was 84 days. Grade IV dermatitis and mucositis was encountered in 2.7% and 1.8% cases respectively, requiring hospitalization. CONCLUSION: Christie regimen for advanced HNSCC is a clinically viable option with acceptable outcomes in a resource constrained setting.

Chemoradiation in elderly patients with head and neck cancers: a single institution experience.

AIMS: To evaluate the efficacy and toxicity of concurrent chemoradiation in patients with head and neck cancers aged 65 and older. MATERIALS AND METHODS: Thirty-two elderly patients were treated with radical chemoradiation. Twenty-six (81.3%) out of thirty-two patients had stage III-IV disease. Twenty-nine (90.6%) patients received concurrent weekly cisplatin or carboplatin, 3 (9.4%) patients received concurrent cetuximab or nimotuzumab. Total dose of radiotherapy ranged from 66Gy to 70Gy. RESULTS: Twenty-nine patients (90.6%) completed at least 5cycles of concurrent chemotherapy. Twenty-four (77.6%) patients achieved complete response. Fourteen (45.2%) patients experienced grade 3 mucositis. None of our patients developed grade 3 or above hematological toxicity. Loco-regional control and overall survival at 2year were 71.6% and 88.9%, respectively. CONCLUSIONS: Chemoradiation in elderly patients with high precision radiotherapy is a feasible option.

Brachytherapy in cancer cervix: Time to move ahead from point A?

Brachytherapy forms an integral part of the radiation therapy in cancer cervix. The dose prescription for intracavitary brachytherapy (ICBT) in cancer cervix is based on Tod and Meredith's point A and has been in practice since 1938. This was proposed at a time when accessibility to imaging technology and dose computation facilities was limited. The concept has been in practice worldwide for more than half a century and has been the fulcrum of all ICBT treatments, strategies and outcome measures. The method is simple and can be adapted by all centres practicing ICBT in cancer cervix. However, with the widespread availability of imaging techniques, clinical use of different dose-rates, availability of a host of applicators fabricated with image compatible materials, radiobiological implications of dose equivalence and its impact on tumour and organs at risk; more and more weight is being laid down on individualised image based brachytherapy. Thus, computed tomography, magnetic-resonance imaging and even positron emission computerized tomography along with brachytherapy treatment planning system are being increasingly adopted with promising outcomes. The present article reviews the evolution of dose prescription concepts in ICBT in cancer cervix and brings forward the need for image based brachytherapy to evaluate clinical outcomes. As is evident, a gradual transition from "point" based brachytherapy to "profile" based image guided brachytherapy is gaining widespread acceptance for dose prescription, reporting and outcome evaluation in the clinical practice of ICBT in cancer cervix.

Proton beam radiotherapy: report of the first ten patients treated at the "Centro Nazionale di Adroterapia Oncologica (CNAO)" for skull base and spine tumours.

PURPOSE: The Italian National Centre for Oncological Hadrontherapy (Centro Nazionale di Adroterapia Oncologica, CNAO), equipped with a proton and ion synchrotron, started clinical activity in September 2011. The clinical and technical characteristics of the first ten proton beam radiotherapy treatments are reported. MATERIALS AND METHODS: Ten patients, six males and four females (age range 27-73 years, median 55.5), were treated with proton beam radiotherapy. After one to two surgical procedures, seven patients received a histological diagnosis of chordoma (of the skull base in three cases, the cervical spine in one case and the sacrum in three cases) and three of low-grade chondrosarcoma (skull base). Prescribed doses were 74 GyE for chordoma and 70 GyE for chondrosarcoma at 2 GyE/fraction delivered 5 days per week. RESULTS: Treatment was well tolerated without toxicity-related interruptions. The maximal acute toxicity was grade 2, with oropharyngeal mucositis, nausea and vomiting for the skull base tumours, and grade 2 dermatitis for the sacral tumours. After 6-12 months of follow-up, no patient developed tumour progression. CONCLUSIONS: The analysis of the first ten patients treated with proton therapy at CNAO showed that this treatment was feasible and safe. Currently, patient accrual into these as well as other approved protocols is continuing, and a longer follow-up period is needed to assess tumour control and late toxicity.

Proton beam radiotherapy: report of the first patient treated at the Centro Nazionale di Adroterapia Oncologica (CNAO) [National Center of Oncologic Hadron Therapy].

Proton beam radiotherapy, an innovative treatment modality, allows delivery of high radiation doses to the target while sparing surrounding healthy structures. The Centro Nazionale di Adroterapia Oncologica (CNAO), equipped with a synchrotron and capable of using both protons and ions, initiated its clinical activity in September 2011. The first treatment of a skull base tumor with protons is reported here. The case of a 26-year-old man with an intracranial low-grade chondrosarcoma of the right petroclival junction is discussed with emphasis on technical and clinical details. Two previous surgical interventions had achieved partial removal of the tumor and the patient was treated with protons for residual disease. The prescribed dose was 70 GyE in 35 fractions of 2 GyE. Treatment was completed with minimal acute toxicity consisting of grade 1 alopecia and nausea. Nine months after treatment the disease is locally controlled. Use of high-energy protons at CNAO is a safe and effective means of treating a tumor located near critical normal structures.

Comparative assessment of doses to tumor, rectum, and bladder as evaluated by orthogonal radiographs vs. computer enhanced computed tomography-based intracavitary brachytherapy in cervical cancer.

PURPOSE: To carry out a comparative assessment of intracavitary brachytherapy (ICBT) doses to tumor, bladder, and rectum based on orthogonal films and contrast enhanced computed tomography (CECT). METHODS AND MATERIALS: Fifty-five ICBT procedures with CT/MRI compatible applicator and CECT scans were evaluated. Doses to Point A, International Commission on Radiation Units and Measurement (ICRU) reference points for maximum bladder (B max(ICRU)) and rectum (R max(ICRU)) localized from orthogonal films were compared with CECT delineated tumor, bladder (B max(CECT)), and rectum (R max(CECT)) doses, respectively. The 95th and 90th percentile bladder (B 95(CECT) and B 90(CECT)) and rectal (R 95(CECT) and R 90(CECT)) doses based on CECT were also estimated. RESULTS: Mean percentage tumor volume encompassed within the prescribed dose of 600 cGy to Point A was 88.8%. Mean B max(ICRU), B max(CECT), R max(ICRU), and R max(CECT) were 631.3 cGy, 1221.4 cGy, 454.8 cGy, and 526.9 cGy, respectively. Paired mean differences were significant between B max(ICRU) and B max(CECT) or B 95(CECT) (both p < 0.001); R max(ICRU) and R max(CECT) (p = 0.005) or R 90(CECT) (p < 0.001), whereas insignificant for B max(ICRU) and B 90(CECT) (p = 0.281), and R max(ICRU) and R 95(CECT) (p = 0.372). CONCLUSIONS: Prescription based on Point A ICBT doses could lead to uncertainty and underdosage in tumor. ICRU 38 maximum bladder and rectal doses significantly underestimate the maximum doses to these organs and represent the 90th and 95th percentile of the maximum doses to these organs, respectively.

Does pretreatment human papillomavirus (HPV) titers predict radiation response and survival outcomes in cancer cervix?--a pilot study.

OBJECTIVE: To evaluate if pretreatment HPV titers in cancer cervix could predict radiation response and survival outcomes. METHODS: Twenty-one patients of cancer cervix were treated by radiotherapy (RT) alone. HPV titers were estimated using DNA Hybrid Capture II test. Loco-regional response at 1 month of RT--complete or partial response (CR and PR respectively) and survival outcomes--local disease-free (LDFS), disease-free (DFS) and overall (OS) survivals were evaluated against pre- and posttreatment HPV titers. RESULTS: Pretreatment HPV titers ranged from 0.81 to 3966.10 RLU/cut off (mean +/- SD: 1264.39 +/- 1148.22, median: 1129.98). Of the demographic features evaluated, mean HPV titers were significantly different only for patients achieving CR or PR at completion of RT (mean +/- SD for CR vs. PR: 1616.31 +/- 1146.86 vs. 384.57 +/- 538.80, P = 0.022). HPV titers at end of RT ranged from 0.12 to 487.42 RLU/cut off (mean +/- SD: 37.31 +/- 108.60, median: 2.33). Patients with higher pretreatment HPV titers (>1000 RLU/cutoff) had a higher CR (P = 0.022) and better survival compared to those with < or =1000 RLU/cutoff (LDFS, P = 0.004; DFS, P = 0.005; OS, P = 0.012). At completion of RT, those having > or =99.5% fall in HPV had superior survival outcomes than those with <99.5% reduction (LDFS, P = 0.002; DFS, P = 0.002; OS, P = 0.004). CONCLUSIONS: Higher pretreatment HPV titers (>1000 RLU/cutoff) could be considered as a predictor of radiotherapy response and survival in cancer cervix. A reduction in these titers to 99.5% of their baseline values at end of radiotherapy is also associated with better survival outcomes.