Radiosensitizing Effect of Curcumin on Human Bladder Cancer Cell Lines: Impact on DNA Repair Mechanisms.

Chemo-radiotherapy is one of the promising approaches to treat bladder cancer, but its effectiveness is limited to sensitive patients. Polyphenol curcumin has shown anticancer and radiosensitizing potentials, but the mechanism is not fully understood. Here, the In Vitro response of UM-UC5 and UM-UC6 bladder cell lines to curcumin and radiation treatments was evaluated. The effect of curcumin on the DNA double-strand breaks repair system after treatment with ionizing radiation (2 Gy) was determined by immunofluorescence. Cell viability, proliferation, and survival were performed using trypan blue, MTT, clonogenic, and sphere-forming assays. The migratory ability of both cells was assessed by wound healing. We showed that curcumin treatment increased the radiosensitivity by modifying the DNA double-strand breaks repair kinetics of the most radioresistant cells UM-UC6 without affecting the radiosensitive UM-UC5. Moreover, UM-UC6 cell survival and proliferation was significantly decreased after the combination of curcumin with radiation. Bladder cell migration was also inhibited considerably. Curcumin was also shown to reduce the number and the volume of bladder cancer spheres of both cell lines. This study revealed that curcumin was able to radiosensitize resistant bladder cell line without affecting the sensitive one with minimal side effects through enhancing DNA damage signaling and repair pathway.

Adjusting the duration of androgen deprivation therapy (ADT) based on nadir PSA for high risk localized prostate cancer patients treated with definitive external beam radiation therapy and ADT.

BACKGROUND: A nadir Prostate-Specific Antigen (nPSA) of 0.06 ng/mL has been shown to be a strong independent predictor of biochemical recurrence-free survival (bRFS) in patients with intermediate or high-risk (HR) prostate cancer treated with definitive external beam radiation therapy (RT) and androgen deprivation therapy (ADT). We aimed to examine the association between the duration of ADT and bRFS in HR localized prostate cancer, based on nPSA. METHODS: Between 1998 and 2015, 204 patients with HR localized prostate cancer were identified. Of them, 157 patients (77.0%) reached the desired nPSA of < 0.06 ng/mL (favorable group), while 47 (23.0%) did not (unfavorable group). Duration of ADT varied among patients depending on physician preference, patient tolerance, and/or compliance. Survival outcomes were calculated using Kaplan-Meier methods and predictors of outcomes using multi-variable cox regression model. RESULTS: In the favorable group, ADT for at least 12 months lead to superior bRFS compared to ≤ 9 months of ADT (P = 0.036). However, no significant difference was seen when examining the value of receiving ADT beyond 12, 18, or 24 months, respectively. On univariate analysis for bRFS, the use of ADT for at least 12 months was significant (P = 0.012) as well as time to nadir PSA (tnPSA), (≤ 6 vs > 6 months); (P = 0.043). The presenting T stage was borderline significant (HR 3.074; 95% CI 0.972-9.719; P = 0.056), while PSA at presentation, Gleason Score and age were not. On multivariate analysis, the use of ADT for 12 months (P = 0.012) and tnPSA (P = 0.037) remained significant. In the unfavorable group, receiving ADT beyond 9 and 12 months was associated with improved bRFS (P = 0.044 and 0.019, respectively). However, beyond 18 months, there was no significant difference. CONCLUSION: In HR localized prostate cancer patients treated with definitive RT and ADT, the total duration of ADT may be adjusted according to treatment response using nPSA. In patients reaching a nPSA below 0.06 ng/mL, a total of 12 months of ADT may be sufficient, while in those not reaching a nPSA below 0.06 ng/mL, a total duration of 18 months is required.

Short-course radiation followed by mFOLFOX-6 plus avelumab for locally-advanced rectal adenocarcinoma.

BACKGROUND: Current standard practice for locally advanced rectal cancer (LARC) entails a multidisciplinary approach that includes preoperative chemoradiotherapy, followed by total mesorectal excision, and then adjuvant chemotherapy. The latter has been accompanied by low compliance rates and no survival benefit in phase III randomized trials, so the strategy of administering neoadjuvant, rather than adjuvant, chemotherapy has been adapted by many trials, with improvement in pathologic complete response. Induction chemotherapy with oxaliplatin has been shown to have increased efficacy in rectal cancer, while short-course radiation therapy with consolidation chemotherapy increased short-term overall survival rate and decreased toxicity levels, making it cheaper and more convenient than long-course radiation therapy. This led to recognition of total neoadjuvant therapy as a valid treatment approach in many guidelines despite limited available survival data. With the upregulation (PDL-1) expression in rectal tumors after radiotherapy and the increased use of in malignant melanoma, the novel approach of combining immunotherapy with chemotherapy after radiation may have a role in further increasing pCR and improving overall outcomes in rectal cancer. METHODS: The study is an open label single arm multi- center phase II trial. Forty-four recruited LARC patients will receive 5Gy x 5fractions of SCRT, followed by 6 cycles of mFOLFOX-6 plus avelumab, before TME is performed. The hypothesis is that the addition of avelumab to mFOLFOX-6, administered following SCRT, will improve pCR and overall outcomes. The primary outcome measure is the proportion of patients who achieve a pCR, defined as no viable tumor cells on the excised specimen. Secondary objectives are to evaluate 3-year progression-free survival, tumor response to treatment (tumor regression grades 0 & 1), density of tumor-infiltrating lymphocytes, correlation of baseline Immunoscore with pCR rates and changes in PD-L1 expression. DISCUSSION: Recent studies show an increase in PD-L1 expression and density of CD8+ TILs after CRT in rectal cancer patients, implying a potential role for combinatory strategies using PD-L1- and programmed-death- 1 inhibiting drugs. We aim through this study to evaluate pCR following SCRT, followed by mFOLFOX-6 with avelumab, and then TME procedure in patients with LARC. TRIAL REGISTRATION: Trial Registration Number and Date of Registration: ClinicalTrials.gov NCT03503630, April 20, 2018.

Survival outcome after radiation therapy for patients with early cervical carcinoma undergoing inadequate primary surgery.

OBJECTIVE: The aim of this study was to investigate the survival outcome after radiation therapy for patients with early cervical carcinoma undergoing inadequate primary surgery. METHODS: A retrospective analysis of medical charts of all patients with stage IA2 to IIA carcinoma who were referred with inappropriate primary surgery and treated with radiation therapy was reviewed. The collected data include age, presenting symptoms, retrospective stage, lymph node status, histology type, type of surgery, baseline radiologic status before radiotherapy, details of radiation therapy, follow-up, and details of disease recurrence, disease-free survival, and overall survival (OS). Kaplan-Meier survival curves were used to show the OS and recurrence-free survival. RESULTS: A total of 32 patients were treated. The median age of the patients was 48.2 years, with a range of 27.6 to 79.2 years. Twenty-three patients had retrospective stage IB1, and 9 had stage IIA disease. The most common type of surgery (62.5%) was total abdominal hysterectomy with or without bilateral salpingo-oophorectomy. The pelvic lymph node dissection (PLND) status was not determined in 20 patients, 11 had PLND surgical assessment (2 were positive), and 1 had bulky PLND by computed tomographic scan.Baseline assessment showed that 14 patients had no residual disease, 11 had microscopic disease, and 7 had macroscopic disease. The follow-up ranged from 3.3 to 77.8 months, with a median of 24.3 months. Eleven patients developed disease recurrence, and all of them died of their disease. Two- and 5-year OS rates were 79% and 51.7%. Univariate analysis did not show a statistically significant effect of either the disease stage or residual disease survival. CONCLUSIONS: Survival outcome after radiation therapy for patients with early-stage cervical cancer undergoing inadequate surgery seems to be markedly worse than that for patients of comparable stage treated initially with radical radiation.

Clinical and Pathological Characteristics of Breast Cancer Among Emirati National Patients.

INTRODUCTION: Breast cancer is the most frequent cancer among Emirati women and is the second leading cause of death among women in the UAE. To date, published studies regarding breast cancer in the UAE have investigated a mixed population of different ethnicities with a low percentage of UAE nationals. This is the first study to highlight the clinical and pathological data of a large cohort of exclusively Emirati national breast cancer patients diagnosed at a tertiary care medical facility. MATERIALS AND METHODS: This is a retrospective study involving breast cancer patients in UAE women who were evaluated and/or treated at the Cleveland Clinic Abu Dhabi during the period from May 2015 until June 2021. RESULTS: This study initially included 372 participants. The median age at diagnosis was 48 years (24-86 years) and 12.3% of patients had screening detected tumors. 30% of patients presented with locally advanced disease and 20% had stage IV disease at presentation. 24% were 40 years or younger at the time of diagnosis. DISCUSSION: To our knowledge, this is the largest study to date focusing exclusively on the presentation and characteristics of Emirati women with breast cancer. The median age of incidence was 48 years and the percentage of patients diagnosed with breast cancer at age 40 or younger years was 24%. This is an agreement with data published in the Middle East, but is significantly below what is reported in Caucasian women in the Western world. In this study, Emirati patients presented with advanced stages of disease. More advanced disease, and higher stage 4 at presentation is another reflection of the low screening rates, but also an indication of a higher patient thresholds for reporting breast health concerns to medical professionals for evaluation. CONCLUSION: Findings of our study do suggest the need to focus efforts on continuing to understand the exact presentation of breast cancer among Emirati women and underscore the need to pursue efforts to improve public education, increase screening utilization and early detection to reduce the burden of disease and address an essential health care need for this unique population.

Effect of bisphosphonates and statins on the in vitro radiosensitivity of breast cancer cell lines.

BACKGROUND: Early-stage breast cancer is usually treated with breast-conserving surgery followed by adjuvant radiation therapy. Acute skin toxicity is a common radiation-induced side effect experienced by many patients. Recently, a combination of bisphosphonates (zoledronic acid) and statins (pravastatin), or ZOPRA, was shown to radio-protect normal tissues by enhancing DNA double-strand breaks (DSB) repair mechanism. However, there are no studies assessing the effect of ZOPRA on cancerous cells. The purpose of this study is to characterize the in vitro effect of the zoledronic acid (ZO), pravastatin (PRA), and ZOPRA treatment on the molecular and cellular radiosensitivity of breast cancer cell lines. MATERIALS: Two breast cancer cell lines, MDA MB 231 and MCF-7, were tested. Cells were treated with different concentrations of pravastatin (PRA), zoledronate (ZO), as well as their ZOPRA combination, before irradiation. Anti-γH2AX and anti-pATM immunofluorescence were performed to study DNA DSB repair kinetics. MTT assay was performed to assess cell proliferation and viability, and flow cytometry was performed to analyze the effect of the drugs on the cell cycle distribution. The clonogenic assay was used to assess cell survival. RESULTS: ZO, PRA, and ZOPRA treatments were shown to increase the residual number of γH2AX foci for both cell lines. ZOPRA treatment was also shown to reduce the activity of the ATM kinase in MCF-7. ZOPRA induced a significant decrease in cell survival for both cell lines. CONCLUSIONS: Our findings show that pretreatment with ZOPRA can decrease the radioresistance of breast cancer cells at the molecular and cellular levels. The fact that ZOPRA was previously shown to radioprotect normal tissues, makes it a good candidate to become a therapeutic window-widening drug.

Post-mastectomy radiation therapy after breast reconstruction: from historic dogmas to practical expert agreements based on a large literature review of surgical and radiation therapy considerations.

Breast reconstruction (BR) after mastectomy is important to consider for a woman's body image enhancement and psychological well-being. Although post-mastectomy radiation (PMRT) significantly improves the outcome of patients with high-risk breast cancer (BC), PMRT after BR may affect cosmetic outcomes and may compromise the original goal of improving quality of life (QoL). With the lack of practical guidelines, it seems essential to work on a consensus and provide some "expert agreements" to offer patients the best option for PMRT after BR. We report a global "expert agreement" that results from a critical review of the literature on BR and PMRT during the 6th international multidisciplinary breast conference in March 2023.

Intraoperative radiation therapy in the management of early stage breast cancer.

Adjuvant radiotherapy (RT) following breast conserving surgery (BCS) is associated with an improvement in local control and a reduction in breast cancer mortality. While traditionally delivered with whole breast irradiation (WBI), novel approaches have looked to reduce the duration, target volume, and toxicity of adjuvant RT. One such approach is intraoperative radiation therapy (IORT), which delivers radiation at the time of surgery with 80-90% of patients not requiring additional WBI. The current review presents IORT techniques and outcomes from modern series evaluating IORT as monotherapy or as a tumor bed boost. Based on two randomized trials (TARGIT-A and ELIOT) with recent updates, concern regarding higher rates of local recurrence with IORT exist, whether using electrons or low-energy techniques. In contrast, data is promising regarding IORT used as a boost, with ongoing studies evaluating its role prospectively. With respect to toxicity, the data suggest IORT is associated with comparable to slightly lower rates of toxicity though there may be a higher risk of seroma requiring aspiration and fat necrosis with IORT. Given current data and guidelines, WBI or other partial breast techniques should remain the standard of care in early stage breast cancer patients, while IORT should not be utilized outside of prospective clinical trials at this time.

Post-lumpectomy radiation therapy boost in breast cancer patients: evidence revisited.

PURPOSE: Radiation therapy is an integral part in the management of breast cancer after breast conservative surgery. In selected patients at high risk for local recurrence (LR), a boost radiation dose is commonly applied to the tumour bed. METHODS: We performed a review of the English literature using PubMed, Medline and Google Scholar for published manuscripts addressing the effect of boost radiation in breast cancer patients, focusing mainly on LR and overall survival (OS). RESULTS: A total of seven studies were included in our review. Most studies (6/7, 85.7%) showed a significant improvement in local control independent of age (hazard ratios ranging between 0.34 and 0.73), with the largest absolute benefit in younger patients. None of the studies, however, was able to demonstrate an improvement in OS. CONCLUSIONS: With lack of sufficient studies addressing the role of boost radiation, individualised treatment decisions are recommended, taking into account the risk factors for LR, including tumour biology. Real-life data are sorely needed to better assess the role of tumour bed boost in the contemporary era.

High rates of advanced prostate cancer in the Middle East: Analysis from a tertiary care center.

OBJECTIVES: Prostate cancer incidence is increasing in the Middle East (ME); however, the data of stage at the diagnosis and treatment outcomes are lacking. In developed countries, the incidence of de novo metastatic prostate cancer ranges between 4% and 14%. We hypothesized that the rates of presentation with advanced disease are significantly higher in the ME based on clinical observation. This study aims to examine the stage at the presentation of patients with prostate cancer at a large tertiary center in the ME. METHODS: After Institutional Review Board approval, we identified the patients diagnosed with prostate adenocarcinoma and presented to a tertiary care center between January 2010 and July 2015. Clinical, demographic, and pathological characteristics were abstracted. Patients with advanced disease were stratified according to tumor volume based on definitions from practice changing clinical trials. Descriptive and Kaplan-Meier survival analysis was used. RESULTS: A total of 559 patients were identified, with a median age at the diagnosis of 65 years and an age range of 39-94 years. Median prostate-specific antigen (PSA) at the presentation was 10 ng/ml, and almost a quarter of the men (23%) presented with metastatic disease. The most common site of metastasis was the bone (34/89, 38%). High-volume metastasis was present in 30.3%, 9%, and 5.2% of the cohort based on STAMPEDE, CHAARTED, and LATITUDE trial criteria, respectively. CONCLUSION: This is the first report showing the high proportion of men from ME presenting with de novo metastasis. This could be due to many factors, including the highly variable access to specialist multidisciplinary management, lack of awareness, and lack of PSA screening in the region. There is a clear need to raise the awareness about prostate cancer screening and early detection and to address the rising burden of advanced prostate cancer affecting men in the ME region.

Complete response of brain metastases from breast cancer overexpressing Her-2/neu to radiation and concurrent Lapatinib and Capecitabine.

Breast cancers that overexpress the human epidermal growth factor receptor 2 (HER-2) have a predilection to metastasize to the brain. Therapeutic options for brain metastases with systemic therapy remain a challenge in those patients since targeted and chemotherapeutic agents have limited penetration through the blood-brain barrier. Here we report the case of a patient with brain metastases from breast cancer overexpressing HER-2 who achieved a complete radiologic response after treatment by radiation and concurrent Lapatinib and Capecitabine.

Comparison of Nodal Target Volume Definition in Breast Cancer Radiation Therapy According to RTOG Versus ESTRO Atlases: A Practical Review From the TransAtlantic Radiation Oncology Network (TRONE).

Regional nodal irradiation has gained interest in recent years with the publication of several important randomized trials and the availability of more conformal techniques. Target volume delineation represents a critical step in the radiation planning process. Adequate coverage of the microscopic tumor spread to regional lymph nodes must be weighed against exposure of critical structures such as the heart and lungs. Among available guidelines for delineating the clinical target volume for the breast/chest wall and regional nodes, the Radiation Therapy Oncology Group and European Society for Radiotherapy and Oncology guidelines are the most widely used internationally. These guidelines have been formulated based on anatomic boundaries of areas historically covered in 2-dimensional field-based radiation therapy but have not been validated by patterns-of-failure studies. In recent years, an important body of data has emerged from mapping studies documenting patterns of local and regional recurrence. We aim to review, discuss, and compare contouring guidelines for breast cancer radiation therapy in the context of contemporary data on locoregional relapse to improve their implementation in modern practice.

Post-Mastectomy Radiation Therapy in Human Epidermal Growth Factor Receptor 2 Positive Breast Cancer Patients: Analysis of the HERA Trial.

PURPOSE: Postmastectomy radiation therapy (PMRT) improves recurrence rates and overall survival in breast cancer patients. However, it remains unclear whether these findings can be applied to human epidermal growth factor receptor 2 (HER-2) positive patients treated with trastuzumab. METHODS AND MATERIALS: The Herceptin Adjuvant (HERA) trial is a phase III randomized clinical trial that established the efficacy of trastuzumab in HER-2 positive early stage breast cancer. The present study is a retrospective analysis of prospective data of 1633 trial patients treated with mastectomy and adjuvant trastuzumab. The primary objective of the study was to determine the effect of PMRT on loco-regional recurrence rates (LRR). Hazard ratios were estimated from Cox models, and LRR curves were generated by the Kaplan-Meier method. RESULTS: Our analysis included 940 patients (57.6%) who received PMRT and 693 patients (42.4%) who did not. Patients in the PMRT group had worse prognostic disease characteristics. At a median follow-up of 11 years, no significant difference in LRR was noted after PMRT in node negative (N0) patients (P = .96). Patients with 1 to 3 positive lymph nodes had a LRR-free survival of 97% in the PMRT group compared with 90% in the no PMRT group (hazard ratio = 0.28, P = .004) and a nonsignificant improved overall survival after PMRT (hazard ratio = 0.63, P = .06). CONCLUSIONS: PMRT delivery in HER-2 positive breast cancer patients with 1 to 3 positive lymph nodes decreases the risk of LRR. Although the magnitude of PMRT benefit is lower than historic studies, the present findings are in favor of PMRT for HER-2 positive breast cancer patients with 1 to 3 involved nodes. Future studies are needed to determine which HER-2 positive breast cancer patients benefit the most from PMRT.

Cystectomy vs. bladder preservation after neoadjuvant chemotherapy in muscle-invasive bladder cancer: A tertiary medical center experience.

BACKGROUND: Radical cystectomy (RC) remains the standard of care for muscle-invasive bladder cancer (MIBC). Because of the higher overall risks associated with RC, particularly in the elderly patients with multiple comorbidities, other less invasive bladder preservation strategies have been considered. METHODS: This is a retrospective chart review of patients diagnosed with MIBC, pT2-4N0-2M0, at the American University of Beirut Medical Center between 2007 and 2017. RESULTS: 98 patients, 85 (86.7%) males and 13 (13.3%) females, were included. Of the 98 patients, 19 (19.3%) patients were treated with upfront CRT, 35 (35.7%) were treated with upfront RC and 44 (45%) were treated with NAC. 26 (26.5%) patients underwent RC after NAC and 18 (18.4%) received CRT after NAC. The mean overall survival (OS) for the different treatment modalities was 69.4, 60.4, 56.1 and 44.2 months for RC, CRT, RC post-NAC and CRT post-NAC, respectively (p = 0.83). The median disease-free survival (DFS) was 29, 22, 21 and 16 months for RC, CRT, RC post-NAC and CRT post-NAC, respectively (p = 0.49). Patients with pT3/T4 had a higher risk of death by 3.335 folds compared to pT2 (95% CI [1.321-8.422], p<0.05). CONCLUSIONS: No difference was noted in the OS and DFS between the groups who underwent RC post-NAC and CRT post-NAC. These findings further support the possibility of bladder preservation after the treatment with NAC for MIBC. The pathologic T stage at diagnosis is an important prognostic factor regardless of treatment modality.

Demographics and outcomes of meningioma patients treated at a tertiary care center in the Middle East.

OBJECTIVE: Meningioma is the most common intracranial primary brain tumor. Risk factors such as age and exposure to radiation as well as prognostic factors such as grade, location, and extent of surgical resection have been reported in the literature worldwide; however, to our knowledge, data from the Middle East is still warranted. In this study, we aim to identify the characteristics, risk factors and outcomes of meningioma patients treated at a multidisciplinary regional referral center in the Middle East. PATIENTS AND METHODS: This is a retrospective chart review with a prospective follow up of outcomes. It included patients diagnosed with meningioma between January 2005 and December 2015 at the American University of Beirut Medical Center. Patient's demographics, risk factors and outcomes were first retrospectively collected. Then, we conducted phone calls to all included alive patients to update their disease status and outcomes. RESULTS: One-hundred and ninety-five patients were included. 69 % had grade I tumors and around 31 % with grades II and III meningiomas. The means of the overall survival and progression free survival (PFS) were 198 and 126 months, respectively. The residence area (city vs. countryside), occupation, alcohol use, oral contraceptive use, family history of meningioma, previous head trauma, radiation exposure for head/brain imaging, cell phone use, and finally, the tumor Ki-67 protein level did not correlate with the survival outcomes. The meningioma grade and extent of resection were significant predictors of the PFS on the univariate analysis, whereas, in the multivariate analysis only previous radiotherapy was significant in prolonging PFS. CONCLUSION: In our study cohort, that included around 30 % grades II and III tumors, previous radiotherapy use was the only significant prognostic factor for longer PFS in patients diagnosed with meningioma. Future prospective studies should be conducted to evaluate genetic and molecular factors that could possibly be linked to meningioma grade and prognosis in our population of Middle Eastern patients.

HPV-related oropharyngeal cancer prevalence in a middle eastern population using E6/E7 PCR.

BACKGROUND: Given the paucity of data and widely variable rates that have been reported, the main objective of this study was to examine the prevalence of HPV-positivity in oropharyngeal squamous cell carcinoma (OPSCC) in Middle Eastern patients presenting to one of the region's largest tertiary care centers using polymerase chain reaction (PCR) amplification of the HPV E6/E7 oncogenes, a highly sensitive and specific method of detection. METHODS: Medical charts and archived pathological specimens were obtained for patients diagnosed with biopsy proven oropharyngeal cancer who presented to the American University of Beirut Medical Center between 1972 and 2017. DNA was extracted from paraffin-embedded specimens and tested for 30 high-risk and low-risk papilloma viruses using the PCR-based EUROarray HPV kit (EuroImmun). RESULTS: A total of 57 patients with oropharyngeal cancer were initially identified; only 34 met inclusion/exclusion criteria and were included in the present study. Most patients were males (73.5%) from Lebanon (79.4%). The most common primary tumor site was in the base of tongue (50%), followed by the tonsil (41.2%). The majority of patients (85.3%) tested positive for HPV DNA. CONCLUSION: The prevalence of HPV-positivity amongst Middle Eastern OPSCC patients, specifically those from Lebanon, may be far greater than previously thought. The Lebanese population and other neighboring Middle Eastern countries may require a more vigilant approach towards HPV detection and awareness. On an international level, further research is required to better elucidate non-classical mechanisms of HPV exposure and transmission.

De-intensifying Radiation Therapy in HER-2 Positive Breast Cancer: To Boost or Not to Boost?

PURPOSE: Radiation therapy is fundamental in the management of breast cancer. After whole breast irradiation, an additional boost dose is often applied to the primary tumor bed. Here, we analyze the effect of radiation therapy boost on local control in patients with HER-2 positive breast cancer. METHODS AND MATERIALS: We studied 1082 patients with HER-2 positive breast cancer who were originally enrolled in the Herceptin Adjuvant Trial and treated with breast-conserving surgery, radiation therapy, and adjuvant chemotherapy with trastuzumab. The primary endpoint of the study was to determine the effect of a radiation boost on local recurrence. Kaplan-Meier curves were generated, and hazard ratios were estimated using Cox regression. RESULTS: Our analysis included 441 patients (40.8%) who received radiation therapy boost and 641 patients (59.2%) who did not, after completion of whole breast radiation. Patients from both groups had similar baseline characteristics in terms of age, nodal involvement, and grade. At a median follow-up of 11 years, local control was 93% (confidence interval, 90%-95%) in the radiation boost group compared with 91% (confidence interval, 89%-93%) in the no-boost group (P = .33). When analyzing patients by age, patients <40 years of age had a higher risk for local recurrence; however, this was not significantly lowered by the addition of boost. Furthermore, no local control benefit for boost was noted in both hormone receptor (HR) subtypes (HR+: P = .11; HR-: P = .98). CONCLUSIONS: Patients with HER-2 positive breast cancer treated with breast-conserving surgery, whole breast radiation, and trastuzumab have excellent local control. Delivery of an additional radiation boost in this patient population was not shown to improve local control. Future studies are needed to identify subgroups of HER-2 positive patients who derive a clinically relevant benefit from radiation boost.

Efficacy and safety-in analysis of short-course radiation followed by mFOLFOX-6 plus avelumab for locally advanced rectal adenocarcinoma.

BACKGROUND: Neoadjuvant chemotherapy and short-course radiotherapy followed by resection has been gaining recognition in the treatment of rectal cancer. Avelumab is a fully human immunoglobulin that binds Programmed Death-Ligand 1 (PD-L1) and prevents the suppression of the cytotoxic T cell immune response. This phase II trial evaluates the safety and pathologic response rate of short-course radiation followed by 6 cycles of mFOLFOX6 with avelumab in patients with locally advanced rectal cancer (LARC). METHODS: This study is prospective single-arm, multicenter phase II trial adopting Simon's two-stage. Short-course radiation is given over 5 fractions to a total dose of 25 Gy. mFOLFOX6 plus avelumab (10 mg/kg) are given every 2 weeks for 6 cycles. Total mesorectal excision is performed 3-4 weeks after the last cycle of avelumab. Follow up after surgery is done every 3 months to a total of 36 months. Adverse event data collection is recorded at every visit. RESULTS: 13 out of 44 patients with LARC were enrolled in the first stage of the study (30% from total sample size). All patients met the inclusion criteria and received the full short-course radiation course followed by 6 cycles of mFOLFOX6 plus avelumab. 12 out of the 13 patients completed TME while one patient had progression of disease and was dropped out of the study. The sample consisted of 9 (69%) males and 4 (31%) females with median age of 62 (33-73) years. The first interim analysis revealed that 3 (25%) patients achieved pathologic complete response (pCR) (tumor regression grade, TRG 0) out of 12. While 3 (25%) patients had near pCR with TRG 1. In total, 6 out of 12 patients (50%) had a major pathologic response. All patients were found to be MMR proficient. The protocol regimen was well tolerated with no serious adverse events of grade 4 reported. CONCLUSION: In patients with LARC, neoadjuvant radiation followed by mFOLFOX6 with avelumab is safe with a promising pathologic response rate. Trial Registration Number and Date of Registration ClinicalTrials.gov NCT03503630, April 20, 2018. https://clinicaltrials.gov/ct2/show/NCT03503630?term=NCT03503630&draw=2&rank=1 .

A review of the international early recommendations for departments organization and cancer management priorities during the global COVID-19 pandemic: applicability in low- and middle-income countries.

Coronavirus disease 2019 (COVID-19) is an infectious disease caused by a new virus that has never been identified in humans before. COVID-19 caused at the time of writing of this article, 2.5 million cases of infections in 193 countries with 165,000 deaths, including two-third in Europe. In this context, Oncology Departments of the affected countries had to adapt quickly their health system care and establish new organizations and priorities. Thus, numerous recommendations and therapeutic options have been reported to optimize therapy delivery to patients with chronic disease and cancer. Obviously, while these cancer care recommendations are immediately applicable in Europe, they may not be applicable in certain emerging and low- and middle-income countries (LMICs). In this review, we aimed to summarize these international guidelines in accordance with cancer types, making a synthesis for daily practice to protect patients, staff and tailor anti-cancer therapy delivery taking into account patients/tumour criteria and tools availability. Thus, we will discuss their applicability in the LMICs with different organizations, limited means and different constraints.

Tongue carcinoma in an adult Down's syndrome patient: a case report.

BACKGROUND: Cancer of the oral cavity is rare and unusual in Down's syndrome patient. The over all risk is similar to that in adult population. CASE PRESENTATION: This case report describes a 27 years old male with Down's syndrome, non-smoker, who developed a poorly differentiated squamous cell carcinoma of the tongue. The patient underwent a hemiglossectomy without neck dissection followed by a postoperative locoregional radiation therapy to a total tumor-bed dose of 56 Gy and 45 Gy to the neck. Three months later, the patient presented with local tongue recurrence and was treated by Docetaxel and Carboplatin chemotherapy with no significant response. The patient died one month later, 9 months after his initial diagnosis. CONCLUSION: To our knowledge, this is the first case of tongue carcinoma arising in a patient with Down's syndrome. This unique case might not be sufficient to make a significant conclusion on the prognosis and survival of these patients but will increase the awareness about this possibility and will help in the appropriate management of Down's syndrome patients.