Role of Oxaliplatin in the Neoadjuvant Concurrent Chemoradiotherapy in Locally Advanced Rectal Cancer: a Review of Evidence.

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.

The state-of-the-art technic of stereotactic radioablation for the treatment of cardiac arrhythmias: An overview.

Introduction: Cardiac arrhythmias, including ventricular tachycardia (VT), stand as a significant threat to health, often leading to mortality and sudden cardiac death. While conventional treatments for VT exhibit efficacy, cases of refractory VT pose challenges. Stereotactic Arrhythmia Radioablation (STAR) offers a novel approach, delivering precise high-dose radiation to well-defined targets with minimal collateral damage. This study explores the potential of STAR as an alternative therapy, especially for high-risk patients or those with refractory VT. Methods: This research reviews ongoing studies and preliminary investigations into the evaluation of the efficacy and safety of STAR. The method involves targeted radiation delivery, assessing reductions in VT recurrence and the early safety profile in refractory VT patients. However, given STAR's early stage and limited clinical evidence, cautious interpretation is advised. Results: Preliminary findings indicate a reduction in VT recurrence with STAR, suggesting promise as a therapeutic option. Early safety profiles are encouraging, but definitive statements on efficacy and safety require further investigation. Positive initial outcomes underscore the need for additional data and long-term studies. Conclusion: Stereotactic Arrhythmia Radioablation is recently emerging as a promising treatment for refractory VT. While early results are encouraging, careful interpretation is needed, due to STAR's early stages. Ongoing investigations are critical for a comprehensive understanding of its long-term efficacy and tolerability. This review provides fundamental insights into STAR's background, principles, pre-treatment procedures, clinical implications, and toxicity, setting the stage for future research in this evolving therapeutic field.

Global, Regional, and National Quality of Care Index (QCI) of Gastric Cancer: A Systematic Analysis for the Global Burden of Disease Study 1990-2017.

BACKGROUND: Gastric Cancer (GC)is the third leading cause of cancer death worldwide. We aimed to compare the quality of care of GC at global, regional, and national levels from 1990 to 2017 in different age, sex, and socio-demographic groups using the quality-of-care index. MATERIAL: METHOD: We used Mortality to Incidence Ratio, DALY to Prevalence Ratio, YLL to YLD Ratio, and Prevalence to Incidence Ratio, that all indicate the quality of care. Then, using Principal Component Analysis (PCA), these values are combined. A new index called QCI (Quality of Care Index), which indicates quality, is introduced to compare the quality of care in different countries in 1990 and 2017. Scores were calculated and scaled 0-100, with higher scores indicating better status. RESULTS: The global QCI of GC in 1990 and 2017 was 35.7 and 66.7, respectively. The QCI index is 89.6 and 16.4 in high and low SDI countries, respectively. In 2017, Japan had the highest QCI with a 100 score. Japan was followed by South Korea, Singapore, Australia, and the United States with 99.5, 98.4, 98.3, and 90.0. On the other hand, the Central African Republic, Eritrea, Papua New Guinea, Lesotho, and Afghanistan with 11.6, 13.0, 13.1, 13.5, and 13.7 had the worst QCI, respectively. CONCLUSION: The quality of care of GC has increased worldwide from 1990 to 2017. Also, higher SDI was associated with more quality of care. We recommend conducting more screening and therapeutic programs for early detection and to improve gastric cancer treatment in developing countries.

Complication and response assessment of high-dose-rate endorectal brachytherapy boost in neo-adjuvant chemoradiotherapy of locally advanced rectal cancer with long-term outcomes.

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 down-staging 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.

Endocervical adenocarcinoma implantation in episiotomy scar: a case report and review of the literature.

BACKGROUND: Cervical cancer is a rare malignancy in the 1st months of pregnancy. Implantation of this cancer in an episiotomy scar is a condition that is rarely reported. CASE PRESENTATION: We reviewed the literature on this condition and reported a 38 year-old Persian patient who had been diagnosed with cervical cancer, clinically stage IB1, 5 months after a term vaginal delivery. She underwent transabdominal radical hysterectomy with ovarian preservation. Two months later she presented with a mass-like lesion in the episiotomy scar which was proved to be of cervical adenocarcinoma origin after biopsy. The patient was scheduled for chemotherapy with interstitial brachytherapy, an alternative to wide local resection, with successful long-term disease-free survival. CONCLUSION: Implantation of adenocarcinoma in an episiotomy scar is a rare occurrence in patients with a history of cervical cancer and previous vaginal delivery near the time of diagnosis which requires extensive local excision as a primary treatment when feasible. The proximity of the lesion to the anus can lead to major complications of extensive surgery. Alternative chemoradiation combined with interstitial brachytherapy can be successful in eliminating cancer recurrence without compromising the functional outcome.

Malignant transformation of tailgut cyst to squamous cell carcinoma, a rare case with poor outcome.

Tailgut cyst, a type of retro-rectal cyst, is a rare condition requiring evaluation for malignant transformation. We report a case of squamous cell carcinoma arising in the retro-rectal cyst, in a 51-year-old female who underwent incomplete resection of the cyst and chemo-radiotherapy, subsequently became locally recurred and metastatic.

Expansion of the quality of care index on breast cancer and its risk factors using the global burden of disease study 2019.

BACKGROUND: Breast cancer (BC), as the top neoplasm in prevalence and mortality in females, imposes a heavy burden on health systems. Evaluation of quality of care and management of patients with BC and its responsible risk factors was the aim of this study. METHODS: We retrieved epidemiologic data of BC from the Global Burden of Disease (GBD) 1990-2019 database. Epidemiology and burden of BC and its risk factors were explored besides the Quality of Care Index (QCI) introduced before, to assess the provided care for patients with BC in various scales. Provided care for BC risk factors was investigated by their impact on years of life lost and years lived with disability by a novel risk factor quality index (rQCI). We used the socio-demographic index (SDI) to compare results in different socio-economic levels. RESULTS: In 2019, 1,977,212 (95% UI: 1,807,615-2,145,215) new cases of BC in females and 25,143 (22,231-27,786) in males was diagnosed and this major cancer caused 688,562 (635,323-739,571) deaths in females and 12,098 (10,693-13,322) deaths in males, globally. The all-age number of deaths and disability-adjusted life years attributed to BC risk factors in females had an increasing pattern, with a more prominent pattern in metabolic risks. The global estimated age-standardized QCI for BC in females in 2019 was 78.7. The estimated QCI was highest in high SDI regions (95.7). The top countries with the highest calculated QCI in 2019 were Iceland (100), Japan (99.8), and Finland (98.8), and the bottom countries were Mozambique (16.0), Somalia (8.2), and Central African Republic (5.3). The global estimated age-standardized rQCI for females was 82.2 in 2019. CONCLUSION: In spite of the partially restrained burden of BC in recent years, the attributable burden to risk factors has increased remarkably. Countries with higher SDI provided better care regarding both the condition and its responsible risk factors.

The role of external beam radiation therapy in the management of thyroid carcinomas: A retrospective study in Iran Cancer Institute.

BACKGROUND: Thyroid cancers are histologically classified into three types; differentiated thyroid carcinoma (DTC), medullary thyroid carcinoma (MTC), and anaplastic thyroid carcinoma (ATC). Among the several therapeutic strategies for treatment and management of thyroid cancer, surgical resection in combination with radioactive iodine therapy (RAI) is indicated for moderate to high-risk differentiated thyroid cancer (DTC) patients- according to current guidelines. However, external radiation therapy (EBRT) can be a viable alternative treatment option for these patients and scarce evidence is available regarding the efficacy and effectiveness of EBRT on thyroid cancer. AIM: This study aims at evaluating the role of EBRT in the management of thyroid carcinomas. METHODS AND RESULTS: In this retrospective cohort study, the records of 59 patients with thyroid cancer were accessed who were treated by EBRT from 2008 to 2016. The indications for EBRT included unresectable primary (definitive) or loco-regional recurrences (salvage) not suitable for RAI, palliation for local disease or metastatic foci (palliative), and the adjuvant treatment for suspected residual disease following resection. Progression-free survival (PFS) and overall survival (OS) were calculated for different types of cancer. PFS was measured from the start of EBRT to the last uneventful follow-up, recurrence, or death. Kaplan-Meier model was used for the survival analysis. Fifty-nine patients were evaluated. The histopathology of the tumors was differentiated and poorly-differentiated, medullary and anaplastic thyroid carcinomas in 22 and 6, 15 and 16 patients, respectively. Twenty-seven patients received external beam radiotherapy (EBRT) as adjuvant therapy and 18 of the cases as palliative therapy while the remaining received salvage or definitive primary EBRT. The stage of patients' cancer was as follows: stage II in 3 and III in 1, IVA in 18 and IVB in 18 and IVC in 19. Stage-based median overall survival was 26 months for IVA, 44 for IVB, and 29 for IVC. The median PFS was 18, 22 and 21 months for stages IVA, IVB and IVC, respectively. CONCLUSION: Based on our findings, EBRT may still play a role in the management of patients with thyroid carcinoma and should be considered in the armamentarium against thyroid cancers.

Duloxetine for the Prevention of Oxaliplatin Induced Peripheral Neuropathy: A Randomized, Placebo-Controlled, Double-blind Clinical Trial.

PURPOSE: Peripheral neuropathy is a dose-limiting adverse effect of oxaliplatin. The aim of this study was to evaluate the efficacy and safety of duloxetine in the prevention of oxaliplatin-induced peripheral neuropathy (OIPN). METHOD: Cancer patients receiving oxaliplatin based chemotherapy were randomized into two arms. Duloxetine 60 mg capsule was given in the first 14 days of each chemotherapy cycle to one arm and placebo was similarly given to another. We compared the two arms based on the incidence of neuropathy and the results of the nerve conduction study (NCS). Grade of complained neuropathy was recorded according to Common Terminology Criteria for Adverse Events (CTCAE). RESULTS: Thirty-two patients mostly rectal cancer (90.6%) were randomized to duloxetine and placebo arms. Highest grade of neuropathy in each cycle was not significantly different between the two groups. Six weeks after treatment incidence of neuropathy of any grade was 52.9 in duloxetine arm compared to 76.9% in placebo arm (P: 0.26). Patients in the duloxetine arm had a lower percentage of chemotherapy cycles (mean) in which they reported distal paresthesia (51% vs. 84%, P = 0.01) and throat discomfort (37% vs. 69%, P = 0.01). Results of NCS were mostly comparable between the two arms except for the velocity in two of the examined nerve which was significantly higher in duloxetine group. Duloxetine was safe and well-tolerated. CONCLUSION: Although a definite conclusion might be difficult to draw but administering duloxetine for 14 days in each chemotherapy cycle could not decrease the incidence of acute OIPN based on CTCAE grading system.

Radiosensitizing effect of dendrosomal nanoformulation of curcumin on cancer cells.

BACKGROUND: Curcumin was found to possess numerous pharmacological activities in clinical research, however, its biological effects together with radiation are yet to be addressed. The present study investigated whether the combined treatment of dendrosomal nanoformulation of curcumin (DNC) and gamma radiation can enhance the radiosensitivity of U87MG and MDA-MB-231 cell lines. METHODS: U87MG and MDA-MB-231 cell lines were exposed to 2 Gray (Gy) and 10 µM DNC determined by MTT assay, then subjected to clonogenic assay, cell cycle assay, and flow cytometric apoptosis analysis. Acridine Orange/Ethidium Bromide (AO/EB) and 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) stained cells were used to study morphologic changes. The expression evaluation of putative cell cycle genes, i.e., P53, P21, CCND1, and CCNB1 was carried out by RT-qPCR. RESULTS: Our findings indicated that the combined treatment with DNC and radiation might cooperatively augment the efficacy of ionizing radiation in the cancer cells and notably decrease the survival and viability of the cells in a time- and concentration-dependent manner. In addition to a synergistic effect deducted by sensitizer enhancement ratio (SER) assessment, co-treatment resulted in greater apoptotic cells than the individual treatments. Further experiments then indicated that DNC could effectively induce G2/M phase cell cycle arrest and apoptosis following irradiation. Conformably, there was a decrement of CCND1 and CCNB1 expression, and an increment of P53, P21 expression. CONCLUSIONS: The data implied that DNC as a radiosensitizer can enhance the lethal effect of ionizing radiation on cancer cells which could be a promising adjuvant therapy in clinical treatments.

Long-term disease-free survival following salvage brachytherapy for recurrent pediatric rhabdomyosarcoma: Two case reports and review of relevant literature.

PURPOSE: Rhabdomyosarcoma (RMS) is the most common pediatric soft-tissue sarcoma, mostly involving the genitourinary (GU) tract, head and neck, and extremities. This study reports the long-term outcome of two infants with recurrent GU-RMS who underwent combination therapy with chemotherapy (ChT) and salvage brachytherapy (BT). METHODS AND MATERIALS: An 18-month-old girl with vaginal bleeding and a 7-month-old boy with urinary retention presented with a diagnosis of vaginal, and bladder/prostate embryonal RMS, respectively. Surgical resection and ChT were done for both patients. However, both developed local recurrences after one year and subsequently, underwent second-line ChT and salvage interstitial high dose rate BT. RESULTS: The clinical target volumes for the first and second patients were treated to a totaldose of 32 Gy in 10 fractions and 35 Gy in 10 fractions, respectively, with two fractions delivered per day with a 6-h interval between fractions. After 9 years of follow-up, both patients are alive with natural growth and no late complication or evidence of recurrence. CONCLUSIONS: Our report shows that BT (for patients with no prior history of irradiation) could result in long-term disease-free survival in well-selected pediatric patients with recurrent GU embryonal RMS without inflicting expected adverse effects of external beam radiotherapy.

Safety and efficacy of salvage high-dose rate brachytherapy for prostate-bed recurrences following radical prostatectomy and external beam radiotherapy.

PURPOSE: This retrospective study aims to evaluate the efficacy and safety of salvage HDR brachytherapy in second local recurrences of prostate cancer after applying radical prostatectomy (RP) and post-operative external beam radiotherapy (EBRT). MATERIALS AND METHODOLOGY: Fifteen patients with locally recurrent prostate cancer after RP and EBRT were salvaged with HDR brachytherapy. Patients had no nodal or distant metastasis evidence on imaging findings, including whole body bone scan, CT scan, and MRI or PSMA PET scan. HDR brachytherapy was applied with 36 Gy in four fractions, in two implantations with 1 week apart. We followed the patients for a control visit every 3 months for 2 years, and every 6 months thereafter. RESULTS: Fifteen patients with the mean age of 64 years (ranged 51-79) underwent salvage HDR brachytherapy. The mean baseline level of PSA was calculated 2.26 ng/ml (ranged from 0.21 to 9, SD = 2.33), which has been significantly decreased in all patients. Hence, two of our patients experienced a biochemical failure during the follow-up period. Our results showed that 86.6% (n = 13) of patients had never experienced a significant increment in PSA level after a median follow-up of 48 months (ranging from 12 to 132 months). Besides, salvage HDR brachytherapy did not induce any significant side effects such as acute or late rectal complications, despite causing urinary complication. CONCLUSIONS: HDR brachytherapy could be considered as a treatment in well-selected patients with the second recurrence in their prostatic bed after the former EBRT allowing for dose escalating to the second nodular recurrence.

Radiosensitization of Glioma Cells by Temozolomide (TMZ): A Colony Formation Assay.

BACKGROUND: Glioblastoma is one of the most radioresistant cancers. It is suggested that combination of radiotherapy with other cancer treatment modalities may increase control of tumor. Temozolomide (TMZ) is one of the most known drugs for glioblastoma. It has shown that TMZ via induction of mutation and cell death can kill glioma cells. OBJECTIVE: In the current study, we aimed to show possible radiosensitization effect of TMZ for glioma cells. In addition, results compared to response of normal fibroblast cells to TMZ and irradiation. MATERIAL AND METHODS: This is in vitro study for evaluation of the effect of TMZ and irradiation on high grade glioma cells and normal fibroblasts. The human fibroblast and glioma cells were cultured as monolayer. The cells were treated with 2000 µM TMZ, which was equal drug dose for IC50%. In addition, irradiation was done with 5Gy gamma rays. The formation of colony was observed following irradiation, treatment with TMZ, and combination both of them. RESULTS: The formation of colony for both glioma and fibroblast cells showed a reduction following irradiation or treatment with TMZ. Irradiation showed more toxicity compared to TMZ for glioma cells, but not fibroblast cells. Combination of TMZ and irradiation showed a significant reduction in the colony formation compared to irradiation or TMZ treatment alone. CONCLUSION: This study showed that TMZ increases sensitivity of both glioma and fibroblast cells to ionizing radiation.

Dose to pelvic lymph nodes during brachytherapy of locally advanced cervical cancer with 60Co HDR source.

PURPOSE: This study investigated the correlation between the prescription dose and dose to the Manchester and International Commission on Radiation Units and Measurements-report 38 (ICRU-38) lymphatic trapezoid points during high-dose-rate (HDR) brachytherapy of locally advanced cervical cancer with (Cobalt-60) 60Co . METHODS AND MATERIALS: A retrospective study was designed for; patients with locally advanced cervical cancer, treated by external beam radiotherapy and concurrent weekly Cisplatin-based chemotherapy, had no extended parametrial invasion and was treated by tandem-ovoid set, from 2017 to 2020. Groupe Européen de Curiethérapie-European Society for Radiotherapy and Oncology (GEC-ESTRO) based target's volume, ICRU-89 revised version of Manchester points A and B, and ICRU-38 lymph node surrogate points were determined, and their dose was recorded. Paired sample t-test, linear regression analysis, and Pearson correlation analyses were done considering a statistical significance level of 0.05 and using IBM SPSS statistics (Version 23, IBM Crop.). RESULTS: Seventy-four brachytherapy cases were included. A positive and strong correlation was observed between D90 of clinical target volume (CTVHR) and points A and B dose for CTVHR〈 15 cc and 〉 35 cc. Strong and significant (p < 0.05) correlations were achieved between pelvic wall points dose and D90 and D100 of the obturator and between D50 and hot points of internal iliac lymph nodes. A strong correlation was obtained between D50 and D90 of external iliac lymph nodes and their ICRU points. CONCLUSIONS: Strong correlations were obtained between dose to the pelvic lymphatic chains and their historical ICRU-38 surrogate points during HDR brachytherapy of locally advanced cervical cancer patients with 60Co tandem-ovoid applicator sets. The correlation strength between point A and prescription dose highly depends on the CTVHR volume.

A comparison between 2D and 3D planning of high-dose-rate vaginal cuff brachytherapy in patients with stage I-II endometrial cancer using cobalt-60.

PURPOSE: Post-surgery radiation can reduce the risk of loco-regional relapse in high-intermediate-risk endometrial cancer. High-dose-rate vaginal cuff brachytherapy (HDR-BRT) is an acceptable method of radiation in majority of endometrial cancer cases. Although 2D planning is frequently used for treatment based on physical examination without any imaging, measurement of the dose received by organs-at-risk (OARs) is not possible. Therefore, the present study was the first to compare dose delivered to target and OARs in 2D vs. 3D planning in patients treated with cobalt-60 source. MATERIAL AND METHODS: In this study, organs including vagina wall, bladder, rectum, and sigmoid were contoured on computed tomography (CT) scan images of 37 endometrial cancer patients, and doses delivered to organs were recorded. Statistics, such as D90, D99, V100, V150, V200, D0.1cc, D1cc, and D2cc were determined. RESULTS: D90 and D99 were lower in 3D treatment planning in comparison with 2D. Although V100 was more in 3D planning, V150 and V200 were less. Analyzing D0.1cc, D1cc, and D2cc of OARs revealed that doses given to rectum, sigmoid, and bladder were less in 3D planning compared to 2D. CONCLUSIONS: Comparison of 2D and 3D planning results showed that 3D planning could deliver an appropriate dose to the target while sparing more OARs.

Current approaches in intensification of long-course chemoradiotherapy in locally advanced rectal cancer: a review.

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 long-course 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.

Low-dose whole-lung irradiation in severe COVID-19 pneumonia: a controlled clinical trial.

INTRODUCTION: The COVID-19 pandemic has caused significant morbidity and mortality thus far. Considering the historical uses of high-voltage X-ray beams for unresolvable pneumonia, we aimed to assess whether low-dose whole-lung irradiation (WLI) could provide any benefits for patients with refractory COVID-19 pneumonia. METHODS: Eleven patients with refractory COVID-19 pneumonia were treated with WLI to a total dose of 1 Gy and compared to 11 patients in a matched control group from June to November 2020. The study's primary endpoint was improvement of chest X-ray severity score (CXRS), followed by changes in mean oxygen (O2) saturation and 28-day mortality as secondary endpoints. RESULTS: The final CXRS was significantly lower in the WLI group (8.7 ± 2.5) compared to the control group (12.3 ± 3.3) (P: 0.016). Change of CXRS from the first to the last chest X-ray was -2.2 ± 3.1 for the WLI group and 0.7 ± 3.9 for the control group, which showed a trend for lower CXRS in the WLI group (U = 30, p: 0.085). Mean O2 saturation showed insignificant improvement in the first 24 hours after radiotherapy (mean difference: 2.5 ± 4.1, Z=-1.6, P value: 0.11). Overall survival after 28 days was 32% in the WLI group and 11% in the control group (P: 0.48). The reason for death in many patients was not merely respiratory failure, but also other adverse situations like pneumothorax, cardiogenic shock and pulmonary thromboembolism. CONCLUSIONS: Low-dose WLI could improve the CXR severity score and O2 saturation in severely ill COVID-19 patients, but larger studies are required to determine its impact on mortality.

Durable complete response to pembrolizumab in microsatellite stable colorectal cancer.

INTRODUCTION: Immunotherapy by checkpoint inhibitors, i.e., anti-programmed death-1(PD-1) or anti-programmed death-ligand 1 (PD-L1) antibodies, has gained more attention managing solid tumors. Pembrolizumab (an anti-PD-1 antibody) in metastatic colorectal cancer (CRC) was approved in 2017 by the US FDA. REASON FOR THE REPORT: Pembrolizumab is not effective in microsatellite stable, mismatch-repair-proficient (MSS-pMMR) molecular phenotype, which comprises most CRC patients. In this report, we present the first case of metastatic CRC with a dramatic and durable response to pembrolizumab despite being of MSS-pMMR phenotype. A 34-year-old woman, presented seven years ago with T3N2bM0 colon cancer and an appendix carcinoid tumor. The last relapse with bilateral pulmonary metastases was refractory to all treatments. Although it seemed unresponsive to immunotherapy because of MSS molecular phenotype, due to the high expression level of PD-L1 (85%), we started treatment with pembrolizumab 200 mg every three weeks and continued for the overall 19 courses. Surprisingly, a rapid and complete response was observed that last until now, i.e., 17 months after discontinuation of pembrolizumab. OUTCOME: Despite non-promising results in the current clinical trials, MSS-pMMR colorectal cancer patients' deprivation from immunotherapy seems not to be reasonable. There are ongoing clinical trials on checkpoint inhibitors either alone or in combination with other drugs. However, immunostaining for PD-L1 should be considered as a possible response predictor. Immunotherapy either by cell-based approaches or by checkpoint inhibitors may revolutionize cancer treatment Pembrolizumab has been approved by the FDA in 2017 for colorectal cancer. However, MSS-pMMR molecular phenotype which comprises the majority of CRC patients, has not shown a good response to checkpoint inhibitors. We present a MSS-pMMR case with complete and durable response to pembrolizumab We suggest immunostaining for PD-L1 as a possible response predictor to checkpoint inhibitors.

Short-course versus long-course neoadjuvant chemoradiotherapy in patients with rectal cancer: preliminary results of a randomized controlled trial.

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: Patients in group I 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 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 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 study groups. Mean duration of radiotherapy in the two groups 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 short-course 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. 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 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.