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Background: Clinical trials investigating the effects of addition of oxaliplatin to neoadjuvant radiochemotherapy in locally advanced rectal cancers (LARCs) have brought controversial results for pathologic complete response as an endpoint. This randomized clinical trial investigated downstaging as a short-term surrogate for progression-free survival (PFS)., Methods: Patients with magnetic resonance imaging (MRI) defined T3, T4 or N+ histologically proven adenocarcinoma of rectum within 15 cm from anal verge were randomly assigned to receive 50-50.4 Gy external beam radiation in 25-28 fractions and concurrent capecitabine 825 mg/m 2 twice daily 5 days a week with or without oxaliplatin 60 mg/m 2 weekly as neoadjuvant radiochemotherapy (Capox and Cap group, respectively). T downstage was defined as at least one stage regression in pathologic report after surgery comparing to MRI image before the preoperative treatment. Adverse effects of treatment were recorded on a weekly basis according to National Cancer Institute Common Toxicity Criteria, version 4., Results: Sixty-three patients were randomly assigned to Cap (n = 31) and Capox (n = 32) groups. There was no grade 4 toxicity. The only grade 3 toxicity that occurred more in Capox group was diarrhea (22% vs 0%; P = 0.006). Histopathologic stage of 52 patients (27 patients in Cap and 25 patients in Capox groups) was compared to their preoperative stage defined by MRI. There was a greater rate of T downstage in Capox group (59% vs 42%; P = 0.037). Eleven patients in Capox group (34%) achieved pathologic complete response, comparing to four in Cap group (13%); P = 0.072., Conclusion: The addition of oxalipatin to neoadjuvant radiochemotherapy in LARC led to higher rate of tumor downstaging. Longer follow-up is needed to evaluate PFS., (© 2017 John Wiley & Sons Australia, Ltd.)

To evaluate the effect of adding neoadjuvant chemotherapy to surgery and radiation therapy for locally advanced resectable oral cavity squamous cell carcinoma, 24 patients with T3 or T4a oral cavity squamous cell carcinoma were randomly assigned to surgery alone or Docetaxel, Cisplatin, and 5-FU (TPF) induction chemotherapy followed by surgery. All patients were planned to receive chemoradiotherapy after surgery. The primary end-points were organ preservation and progression-free-survival. SPSS version 17 was used for data analysis. Median follow-up was 16 months. The median age of the patients was 62 years old (23-75 years). Man/woman ratio was 1.13. The primary site of the tumor was the tongue in most patients (48%). No significant difference was observed between pathologic characteristics of the two groups. Chemotherapy group showed 16% complete pathologic response to TPF. No significant difference in organ preservation surgery or overall survival was detected. However, the patients in the chemotherapy group had longer progression-free-survival (P=0.014). Surgery followed by chemoradiotherapy with or without TPF induction results in similar survival time. However, progression-free-survival improves with the TPF induction chemotherapy. Studies with more patents and new strategies are recommended to evaluate organ preservation improvement and long-term outcomes.

Background: Evidence suggests that statins can improve survival outcomes and ameliorate treatment-related side-effects in certain malignancies. Statins exhibit various mechanisms of action, including apoptosis induction, proliferation inhibition, tumor radiosensitization, lipid production suppression, and anti-inflammatory effects. This trial aimed to assess the impact of lovastatin on patients with locally advanced head and neck squamous cell carcinoma (HNSCC) undergoing definitive chemoradiation. Method: In this double-blinded randomized phase 2 clinical trial, 35 patients were randomly allocated to receive either 80 mg of lovastatin daily in conjunction with chemoradiotherapy (case group, n=18) or a placebo (control group). Primary outcomes included the response rate (RR) after three months, the occurrence of acute/late side-effects, median progression-free survival (PFS), and overall survival (OS). Results: The complete RR was slightly higher in the statin group (83.3% vs. 64.7%), although it did not reach statistical significance (P = 0.592). Acute adverse events did not significantly differ between the two groups. Grade 3 dermatitis occurred more frequently in the placebo group (35.3% vs. 11.1%), while grade 3 mucositis was more common in the statin group (38.9% vs. 11.8%). The median OS was 22 months (confidence interval (CI) 95% = 6.3-37.6) in the statin group and 17 months (CI 95% = 4.9-29.1) in the control group (P = 0.50). Median PFS was 20 months (CI 95% = 15.8-24.1) in the statin group and 15 months (CI 95% = 8.2-21.7) in the control group (P = 0.609). Conclusion: Combining lovastatin with chemoradiation augments the therapeutic effect in HNSCC. Larger-scale studies incorporating advanced radiotherapy techniques and baseline lipid profile assessments are necessary to investigate statins' efficacy in HNSCC further. [ABSTRACT FROM AUTHOR]

Purpose: To identify efficacy, complication, and pathologic response of high-dose-rate endorectal brachytherapy (HDR-BRT) boost in neo-adjuvant chemoradiotherapy (nCRT) of locally advanced rectal cancer. Material and methods: Forty-four patients who met eligibility criteria were included in this non-randomized comparative study. Control group was recruited retrospectively. nCRT (50.40 Gy/28 fr. plus capecitabine 825 mg/m2 twice daily) was administered to both groups before surgery. In the case group, HDR-BRT (8 Gy/2 fr.) was supplemented after chemoradiation. Surgery was done 6-8 weeks after completion of neo-adjuvant therapy. Pathologic complete response (pCR) was the study's primary endpoint. Results: From 44 patients in the case and control groups, pCR was 11 (50%) and 8 (36.4%), respectively (p = 0.27). According to Ryan's grading system, tumor regression grade (TRG) TRG1, TRG2, and TRG3 were 16 (72.7%), 2 (9.1%), and 4 (18.2%) in the case, and 10 (45.5%), 7 (31.8%), and 5 (22.7%) in the control group (p = 0.118). T down-staging was found in 19 (86.4%) and 13 (59.1%) patients in the case and control groups, respectively. No grade > 2 toxicity was identified in both the groups. Organ preservation was achieved in 42.8% and 15.3% in the case and control arm (p = 0.192). In the case group, 8-year overall survival (OS) and disease-free survival (DFS) were 89% (95% CI: 73-100%) and 78% (95% CI: 58-98%), respectively. Our study did not reach median OS and median DFS. Conclusions: Treatment schedule was well-tolerated, and neo-adjuvant HDR-BRT could achieve better T downstaging as a boost comparing with nCRT, without significant complication. However, the optimal dose and fractions in the context of HDR-BRT boost needs further studies. [ABSTRACT FROM AUTHOR]

Background: Hypopharyngeal carcinoma (HPC) is a rare head and neck cancer which poses many therapeutic challenges. There is limited evidence regarding the outcomes of HPC treatment in Iran. Method: In this retrospective cohort study, we evaluated patients treated with chemoradiation or radiation alone, between 2007 and 2016 in the radiation oncology ward of the cancer institute affiliated to Tehran University of Medical Sciences. The design of the study was reviewed and approved by the local institutional review board (code: 86100142). All patients underwent definitive radiotherapy with or without concurrent or sequential chemotherapy. We assessed the two-year overall survival (OS) as the primary outcome. The progression-free survival (PFS) was our secondary outcome. Results: We studied 40 patients whose median age was 58 years. 37 patients were stage 3 or 4, while the most common stage was T3N1-2, observed in 35% of the cases. The most common site of involvement was pyriform sinus (47.5%). The twoyear OS rate was 29%. The two-year PFS was 22%. In the univariate analysis, N0-1 vs. N 2-3 and stage 2 vs. stage 3-4 were significant predictors of OS. In addition, distant metastasis had almost a significant association with lower OS. Conclusion: The outcome of locally advanced HPC was not promising using 3DCRT alone. It is necessary to implement dramatic changes in the management of these patients to achieve better outcomes. [ABSTRACT FROM AUTHOR]

Background: Iran is a high-risk area with a poor prognosis for esophageal cancer. We conducted the present study to evaluate the survival rate of esophageal cancer after the introduction of neo-adjuvant chemo-radiation at the Cancer Institute of Iran. Method: We performed a retrospective cohort study and abstracted the data of 421 patients who referred to the Cancer Institute of Iran between 2007 and 2011. Life table and Kaplan-Meier approaches were applied to estimate 1-, 3-, and 5-year survival rates and corresponding 95% confidence intervals (CI). Multiple Cox regression model was recruited for investigating the association between 5-year survival rate and prognostic factors. Results: We found that 1-, 3-, and 5-year survival rates were 66.7%, 28.2, and 20.9%, respectively. The hazard ratio (HR) was significantly higher among the patients who has received definitive chemo-radiation therapy (Hazard ratio (HR) = 2.2, 95% confidence interval (CI): 1.1, 4.2), surgery (HR= 2.0 95% CI: 1.0, 3.7), and palliative care (HR= 4.2, 95% CI: 2.1, 1.8) compared with those who received neo-adjuvant chemo-radiation and surgery. We also found that the 5-year survival rate was doubled in the current study conducted between 2007 and 2011 (20.9%) compared with the previous one conducted between 1997 and 2006 (10.0%). Additionally, a considerable improvement was observed in 1- and 3-year survival rate of esophageal cancer at the Cancer Institute of Iran. Conclusion: Following the administration of neo-adjuvant chemo-radiation therapy, the prognosis of esophageal cancer has improved significantly at the Cancer Institute of Iran during the last decade. More data from other cancer centers and provinces of Iran are required. [ABSTRACT FROM AUTHOR]

Rectal cancer is one of the most prevalent cancers in the world. In many countries, the current standard of care is long-course chemoradiation (CRT), followed by total mesorectal excision. Some efforts have been made by intensifying radiation or chemotherapy components of the neoadjuvant therapy to further decrease the local recurrence and augment surgery's feasibility and improve the oncological outcomes. This paper reviews recent intensified neoadjuvant interventions in locally advanced rectal cancer (LARC) in terms of efficacy and treatment-related toxicity. Many maneuvers have been made so far to improve the oncological outcomes of rectal cancer with intensified neoadjuvant longcourse CRT. Some of these approaches seem compelling and deserve further study, while some have just increased the treatment-related toxicities without evident benefits. Those endeavors with greater pathological complete response than the standard of care may make us await the long-term results on survival rates and chronic treatment-related toxicity. After introduction of neoadjuvant CRT for LARC there have been many efforts to improve its outcomes. Here, this study gathered most of these efforts that intensified the neoadjuvant therapy with some being promising and some being futile. [ABSTRACT FROM AUTHOR]

Background: Cyclo-oxygenase-2 (COX-2), an enzyme induced in pathological states, mediates the production of prostaglandins. Celecoxib as a selective COX-2 inhibitor may affect the outcome of treatments in several cancer types. Objectives: We conducted a randomized controlled double-blind clinical trial to evaluate the toxicity and efficacy of celecoxib administered concurrently with chemoradiation in locally advanced head and neck carcinomas. Methods: Patients with locally advanced head and neck carcinoma referred for definitive chemoradiation were eligible to enter the study. Celecoxib (100mg, qid, oral) or placebo was administered all over the chemoradiation period. Results: Totally, 122 patients were enrolled. Patients in the celecoxib group had a longer median time to onset of grade 2 mucositis (56 days vs. 28 days, P < 0.001) and a lower rate of grade 3 mucositis (1.6% vs. 21.3%, P = 0.001). The 4-year progression-free survival was significantly higher in the celecoxib group (P = 0.0013). Conclusions: This study revealed that utilizing celecoxib may lead to better tumor local control and delayed and reduced mucosal side effects of chemoradiation. [ABSTRACT FROM AUTHOR]

Purpose: Colorectal cancer is becoming an increasing concern in the middle-aged population of Iran. This study aimed to compare the preliminary results of short-course and long-course neoadjuvant chemoradiotherapy treatment for rectal cancer patients. Materials and Methods: In this clinical trial we recruited patients with rectal adenocarcinoma located from 5 cm to 15 cm above the anal verge. Patients in group I (short-course) received three-dimensional conformational radiotherapy with a dose of 25 Gy/5 fractions in 1 week plus concurrent XELOX regimen (capecitabine 625 mg/m² from day 1-5 twice daily and oxaliplatin 50 mg/m² on day 1 once daily). Patients in group II (long-course) received a total dose of 50-50.4 Gy/25-28 fractions for 5 to 5.5 weeks plus capecitabine 825 mg/m² twice daily. Both groups underwent consolidation chemotherapy followed by delayed surgery at least 8 weeks after radiotherapy completion. The pathological response was assessed with tumor regression grade. Results: In this preliminary report on complications and pathological response, 66 patients were randomized into two study groups. Mean duration of radiotherapy in the group II (long-course) was 5 ± 1 days (range, 5 to 8 days) and 38 ± 6 days (range, 30 to 58 days). The median follow-up was 18 months. Pathological complete response was achieved in 32.3% and 23.1% of patients in the shortcourse and long-course groups, respectively (p = 0.558). Overall, acute grade 3 or higher treatment- related toxicities occurred in 24.2% and 22.2% of patients in group I and II, respectively (p = 0.551). No acute grade 4 or 5 adverse events were observed in either group except one grade 4 hematologic toxicity that was seen in group II. Within one month of surgery, no significant difference was seen regarding grade =3 postoperative complications (p = 0.333). Conclusion: For patients with rectal cancer located at least 5 cm above the anal verge, short-course radiotherapy with concurrent and consolidation chemotherapy and delayed surgery is not different in terms of acute toxicity, postoperative morbidity, complete resection, and pathological response compared to long-course chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Background Clinical trials investigating the effects of addition of oxaliplatin to neoadjuvant radiochemotherapy in locally advanced rectal cancers (LARCs) have brought controversial results for pathologic complete response as an endpoint. This randomized clinical trial investigated downstaging as a short-term surrogate for progression-free survival (PFS). Methods Patients with magnetic resonance imaging (MRI) defined T3, T4 or N+ histologically proven adenocarcinoma of rectum within 15 cm from anal verge were randomly assigned to receive 50-50.4 Gy external beam radiation in 25-28 fractions and concurrent capecitabine 825 mg/m2 twice daily 5 days a week with or without oxaliplatin 60 mg/m2 weekly as neoadjuvant radiochemotherapy (Capox and Cap group, respectively). T downstage was defined as at least one stage regression in pathologic report after surgery comparing to MRI image before the preoperative treatment. Adverse effects of treatment were recorded on a weekly basis according to National Cancer Institute Common Toxicity Criteria, version 4. Results Sixty-three patients were randomly assigned to Cap ( n = 31) and Capox ( n = 32) groups. There was no grade 4 toxicity. The only grade 3 toxicity that occurred more in Capox group was diarrhea (22% vs 0%; P = 0.006). Histopathologic stage of 52 patients (27 patients in Cap and 25 patients in Capox groups) was compared to their preoperative stage defined by MRI. There was a greater rate of T downstage in Capox group (59% vs 42%; P = 0.037). Eleven patients in Capox group (34%) achieved pathologic complete response, comparing to four in Cap group (13%); P = 0.072. Conclusion The addition of oxalipatin to neoadjuvant radiochemotherapy in LARC led to higher rate of tumor downstaging. Longer follow-up is needed to evaluate PFS. [ABSTRACT FROM AUTHOR]

Background: Colorectal carcinoma is one of most common cancers in Iran with increasing incidence. The mean age of the affected is decreasing. With progresses in multimodality treatment, we witnessed improved prognosis in colorectal cancers. Objectives: This study aimed at evaluating the outcomes of patients with rectal adenocarcinoma treated with neoadjuvant chemoradiotherapy followed by surgery. Methods: In this retrospective cohort study, we assessed the oncologic treatment outcomes of patients with locally advanced (T3-4 or N+ve) rectal adenocarcinoma in our high volume cancer center, Iran cancer institute, Tehran, Iran. Patients with synchronous metastasis, previous malignancy, and history of pelvic radiation were excluded. The primary endpoint was overall survival (OS) rate and secondary endpoints were disease-free survival and pathologic response. Results: Of patients being treated between 2008 and 2014, 158 were entered to final analysis; they completed planned neoadjuvant treatment and retuned after surgery with pathology report. The mean age was 56 years and mean interval from radiotherapy to surgery was 9 weeks. Thirty percent achieved pathologic complete response. Two-year overall and disease-free survival rate was 87% and 80%, respectively. In multivariate analysis age, sex, local recurrence, clinical stage, and radiotherapy to surgery interval failed to predict OS. The pathologic response (complete vs. non-complete) and the absence of distant metastasis were independent predictors of OS. Conclusions: The rate of pathologic response and survival in our series was comparable to other big randomized studies in the world and even better than previous national reports. These findings emphasize the necessity of treating patients with locally advanced rectal cancer in high volume centers. [ABSTRACT FROM AUTHOR]

Background: The current standard of adjuvant management for gastric cancer after curative resection based on the results of intergroup 0116 is concurrent chemoradiation. Current guidelines for designing these challenging fields still include two-dimensional simulation with simple AP-PA parallel opposed design. However, the implementation of radiotherapy (RT) remains a concern. Our objective was to compare three-dimensional (3D) techniques to the more commonly used AP-PA technique. Methods: A total of 24 patients with stages II-IV adenocarcinoma of the stomach were treated with adjuvant postoperative chemoradiation with simple AP-PA technique, using Cobalt-60. Total radiation dose was 50.4Gy. Landmark-based fields were simulated to assess PTV coverage. For each patient, three additional radiotherapy treatment plans were generated using three-dimensional (3D) technique. The four treatment plans were then compared for target volume coverage and dose to normal tissues (liver, spinal cord, kidneys) using dose volume histogram (DVH) analysis. Results: The three-dimensional planning techniques provided 10% superior PTV coverage compared to conventional AP-PA fields (p<0.001). Comparative DVHs for the right kidney, left kidney and spinal cord demonstrate lower radiation doses using the 3D planning techniques (p<0.0001), the liver dose is higher (p=0.03), but is still well below liver tolerance. Conclusion: Despite the department protocol using conventional planning, 3D radiotherapy provides 10% superior PTV coverage. It is associated with reduced radiation doses to the kidneys and spinal cord compared to AP-PA techniques with the potential to reduce treatment toxicity. [ABSTRACT FROM AUTHOR]

The treatment of locally advanced rectal cancer (LARC) is a challenging situation for radiation oncologists and colorectal surgeons. Most current approaches recommend neoadjuvant fluorouracil or capecitabine-based chemoradiotherapy followed by surgery as a standard of care. Intensification of concurrent chemotherapy by adding oxaliplatin to fluorouracil or capecitabine backbone to get better outcomes is the matter that has remained unresolved. In this review, we searched Medline and Google Scholar databases and selected 28 prospective phase II and III clinical trials that addressed this question. We discussed the potential advantages and drawbacks of incorporating oxaliplatin into concurrent chemoradiation therapy. We tried to define whether adding oxaliplatin to concurrent chemoradiation with excellent performance and high-risk features benefits some subpopulations. The available literature suggests that by adding oxaliplatin there are some benefits in enhancing response to neoadjuvant chemoradiotherapy, however, without any translated improvements in long-term outcomes including overall and disease-free survival. [ABSTRACT FROM AUTHOR]