ABSTRACT
BACKGROUND: Nasopharyngeal carcinoma (NPC) is a head and neck cancer more frequent among East Asian populations compared with Western populations. While much is known about human papillomavirus's (HPV's) role in oropharyngeal cancer (OPC), little is known about its prevalence and prognostic value in NPC. The aim of this study is to investigate the role of HPV in NPC treated with definitive radiotherapy at a single institution. METHODS: A retrospective cohort analysis of patient's medical records and HPV status treated for NPC in Rambam Health Care Campus (Rambam HCC). Immunohistochemical staining for p16 was used as a surrogate marker of HPV infection in the tumor cells. All specimens were stained and evaluated by pathologists at the referring center independently. RESULTS: In total, 87 patients diagnosed with NPC were treated at Rambam HCC between 2005 and 2018. Seventy-four patients had accessible data on the disease's clinical parameters and p16 status. In total, 10/74 (13.5%) had p16-positive staining in tumor cells; 75% were men and over 50% were smokers. The average age of diagnosis for the whole cohort was 48 years, being lower for p16-positive patients compared with p16-negative patients at 43 and 49 years old, respectively. A total of 84% of the patients had advanced disease of stage III and IV at presentation. Only 16% were diagnosed with stage I and II. Unlike the p16-negative group, the p16-positive group did not include any stage I or II disease. In univariate and multivariate analysis of overall survival rates, the age at diagnosis and the nodal spread status were the only statistically significant measures. P16 status was not found to be associated with survival. CONCLUSIONS: The HPV prevalence in NPC is nontrivial. p16-positive patients had significantly less nodal spread and tended to be younger. Both age and nodal status were significantly correlated with the survival, but P16 status was not prognostic. Further large-scale trials are needed to elucidate the role of HPV in NPC.
ABSTRACT
Background and Objective: Surgery is still considered the mainstay of treatment of locally advanced rectal cancer (LARC). Nevertheless, "curable" disease may still pose a great risk for both local and distant relapses. Since the early eighties of the past century, we have witnessed mounting evidence supporting the multi-modality approach to tackle this disease effectively. The multi-modality approach is variable between different positive trials. In this review, we discuss the treatment evolution of LARC, highlighting the key differences between the different contemporary strategies utilized. Based on current evidence, we sought to define distinct patient subgroups and to propose a treatment algorithm that best fits patient's risk. Methods: We conducted a literature search through PubMed and Google scholar. Eligible papers were phase 2/3 trials [in organ preservation (OP), observational and retrospective studies were also acceptable] published in English. We used keywords such as "locally advanced rectal cancer", "perioperative therapy in rectal cancer", "short course radiotherapy", "chemoradiation in rectal cancer", "interval to surgery", "Neoadjuvant therapy", "Organ preservation" and "Total neoadjuvant treatment [TNT]". Key Content and Findings: Various trials consistently demonstrated the benefit of preoperative radiotherapy in LARC, the role of adjuvant chemotherapy is controversial based on published studies, TNT was associated with a risk reduction in distant metastasis, and more reassuring evidence is accumulating regarding OP. Conclusions: The treatment landscape of LARC is rapidly changing. Clinicians should carefully tailor treatment strategy based on patient's risk.
ABSTRACT
PURPOSE: Neoadjuvant chemoradiation followed by surgery is the current standard of care in the treatment of locally advanced rectal cancer. Those who achieved pathologic complete response, following this standard of care, complete pathologic response (pCR) had better outcome. Until now there are no reliable clinical parameters to predict this response. The purpose of the study was to evaluate whether tumor volume may serve as a predictive factor in patients treated with neoadjuvant chemoradiotherapy. MATERIALS AND METHODS: Between September 2015 and September 2019, patients diagnosed with stage IIA to IIIC rectal adenocarcinoma, who were treated with neoadjuvant chemoradiation, were enrolled to this study. All patients underwent rectal ultrasound, pelvic magnetic resonance imaging, fluorodeoxyglucose-positron emission tomography-computed tomography and the diagnosis was confirmed by pathology report. Radiation therapy was consisted of 50 Gy delivered to the tumor site, 2 Gy a day, 5 times a week and to the pelvic lymph nodes for a total of 45 Gy in 1.8 Gy a day, 5 times a week. The gross tumor volume (GTV) was contoured by radiation oncology expert, reviewed by radiology and nuclear medicine expert and approved by radiation therapy tumor board. Chemotherapy was consisted of either capecitabine 875 mg/m2 twice a day or continuous. IV infusion of 5 fluorouracil 375 mg/m2 for 4 consecutive days in a 3 weeks apart. Operation, either low anterior or abdominoperineal resection was carried out 6 to 8 weeks following completion of treatment. Patients were assigned to either complete pathologic response (pCR) or non-pCR groups. GTV, among other clinical and treatment parameters, were evaluated for prediction of pCR. Statistical methods included independent t test, logistic regression, area under the curve-receiver operating characteristic, Bayesian independent statistics and multilayer perceptron model. RESULTS: One hundred ninety-three patients were enrolled to this study, 6 were excluded due to metastatic disease detected at the time of operation. Seventy had stage II and 117 had stage III. Forty-four of 187 (23.5%) patients achieved pCR and 143 patients had either partial or no response/progressive disease. Among the 44 pCR group, 21 had stage II and 23 had stage III disease. Treatment interruption, defined as either a delay of up to 1 week in radiation, and a dose reduction to 75%, was occurred in 42 patients. Sex, ethnicity, distance from anal verge to tumor, height, weight, age, delivered radiation dose, radiotherapy techniques, clinical T and N stage and GTV were evaluated for prediction of pCR. GTV at the volume of <39.5 cm3 was the only significant predictive factor to detect pCR by logistic regression model (P<0.01) and by Bayesian independent test (P=0.026). Area under the receiver operating characteristic curve of GTV <39.5 cm3 showed area under the curve of 0.715 (P=0.009) for stage II and area under the curve of 0.62 (P>0.05) for stage III. CONCLUSION: GTV may serve as a predictive factor for achieving pCR in locally advanced rectal cancer after neoadjuvant chemoradiotherapy.
