Good clinical practice and the use of hypofractionation radiation schedules as weapons to reduce the risk of COVID-19 infections in radiation oncology unit: A mono-institutional experience.

BACKGROUND: After coronavirus disease outbreak emerged in 2019, radiotherapy departments had to adapt quickly their health system and establish new organizations and priorities. The purpose of this work is to report our experience in dealing with COVID-19 emergency, how we have reorganized our clinical activity, changed our priorities, and stressed the use of hypofractionation in the treatment of oncological diseases. MATERIALS AND METHODS: The patients' circuit of first medical examinations and follow-up was reorganized; a more extensive use of hypofractionated schedules was applied; a daily triage of the patients and staff, use of personal protective equipment, hand washing, environment sanitization, social distancing and limitations for the patients' caregivers in the department, unless absolutely essential, were performed; patients with suspected or confirmed COVID-19 were treated at the end of the day. In addition, the total number of radiotherapy treatment courses, patients and sessions, in the period from February 15 to April 30, 2020, comparing the same time period in 2018 were retrospectively investigated. In particular, changes in hypofractionated schedules adopted for the treatment of breast and prostate cancer and palliative bone metastasis were analyzed. RESULTS: Between February 15, and April 30, 2020, an increased number of treatments was carried out: Patients treated were overall 299 compared to 284 of the same period of 2018. Stressing the use of hypofractionation, 2036 RT sessions were performed, with a mean number of fractions per course of 6.8, compared to 3566 and 12.6, respectively, in 2018. For breast cancer, the schedule in 18 fractions has been abandoned and treatment course of 13 fractions has been introduced; a 27% reduction in the use of 40.5 Gy in 15 fractions, (67 treatments in 2018-49 in 2020) was reported. An increase of 13% of stereotactic body radiation therapy for prostate cancer was showed. The use of the 20 Gy in 4 or 5 sessions for the treatment of symptomatic bone metastasis decreased of 17.5% in favor of 8 Gy-single fraction. Three patients results COVID-19 positive swab: 1 during, 2 after treatment. Only one staff member developed an asymptomatic infection. CONCLUSIONS: The careful application of triage, anti-contagion and protective measures, a more extensive use of hypofractionation allowed us to maintain an effective and continuous RT service with no delayed/deferred treatment as evidenced by the very low number of patients developing COVID-19 infection during or in the short period after radiotherapy. Our experience has shown how the reorganization of the ward priority, the identification of risk factors with the relative containment measures can guarantee the care of oncological patients, who are potentially at greater risk of contracting the infection.

Moderately Hypofractionated Helical Tomotherapy for Prostate Cancer: Ten-year Experience of a Mono-institutional Series of 415 Patients.

BACKGROUND/AIM: Radiotherapy represents an important therapeutic option in the management of prostate cancer (PCa). As helical tomotherapy may improve toxicity outcomes, we aimed to evaluate and report the toxicity and clinical outcomes of localized PCa patients treated with moderately hypofractionated helical tomotherapy. PATIENTS AND METHODS: We retrospectively analyzed 415 patients affected by localized PCa and treated with moderately hypofractionated helical tomotherapy in our department from January 2008 to December 2020. All patients were stratified according to the D'Amico risk classification: low-risk 21%, favorable intermediate-risk 16%, unfavorable intermediate-risk 30.4%, and high-risk 32.6%. The dose prescription for high-risk patients was 72.8 Gy to the prostate (planning tumor volume-PTV1), 61.6 Gy to the seminal vesicles (PTV2), and 50.4 Gy to the pelvic lymph nodes (PTV3) in 28 fractions; for low- and intermediate-risk patients 70 Gy for PTV1, 56 Gy for PTV2, and 50.4 Gy for PTV3 in 28 fractions. Image-guided radiation therapy was performed daily in all patients by mega-voltage computed tomography. Forty-one percent of patients received androgen deprivation therapy (ADT). Acute and late toxicity was assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events v.5.0 (CTCAE). RESULTS: Median follow-up was 82.7 months (range=12-157 months) and the median age of patients at diagnosis was 72.5 years (range=49-84 years). The 3, 5, and 7 yr overall survival (OS) rates were 95%, 90%, and 84%, respectively, while 3, 5, and 7 yr disease-free survival (DFS) were 96%, 90%, and 87%, respectively. Acute toxicity was as follows: genitourinary (GU) G1 and G2 in 35.9% and 24%; gastrointestinal (GI) in 13.7% and 8%, with G3 or more acute toxicities less than 1%. The late GI toxicity G2 and G3 were 5.3% and 1%, respectively, and the late GU toxicity G2 and G3 were 4.8% and 2.1%, respectively, and only three patients had a G4 toxicity. CONCLUSION: Hypofractionated helical tomotherapy for PCa treatment appeared to be safe and reliable, with favorable acute and late toxicity rates and encouraging results in terms of disease control.

Efficacy and Tolerability of Perampanel in Brain Tumor-Related Epilepsy: A Systematic Review.

(1) Background: Epilepsy is a frequent comorbidity in patients with brain tumors, in whom seizures are often drug-resistant. Current evidence suggests that excess of glutamatergic activity in the tumor microenvironment may favor epileptogenesis, but also tumor growth and invasiveness. The selective non-competitive α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist perampanel (PER) was demonstrated to be efficacious and well-tolerated in patients with focal seizures. Moreover, preclinical in vitro studies suggested a potential anti-tumor activity of this drug. In this systematic review, the clinical evidence on the efficacy and tolerability of PER in brain tumor-related epilepsy (BTRE) is summarized. (2) Methods: Five databases and two clinical trial registries were searched from inception to December 2022. (3) Results: Seven studies and six clinical trials were included. Sample size ranged from 8 to 36 patients, who received add-on PER (mean dosage from 4 to 7 mg/day) for BTRE. After a 6-12 month follow-up, the responder rate (% of patients achieving seizure freedom or reduction ≥ 50% of seizure frequency) ranged from 75% to 95%, with a seizure freedom rate of up to 94%. Regarding tolerability, 11-52% of patients experienced non-severe adverse effects (most frequent: dizziness, vertigo, anxiety, irritability). The retention rate ranged from 56% to 83%. However, only up to 12.5% of patients discontinued the drug because of the adverse events. (4) Conclusions: PER seems to be efficacious, safe, and well-tolerated in patients with BTRE. Further randomized studies should be conducted in more homogeneous and larger populations, also evaluating the effect of PER on tumor progression, overall survival, and progression-free survival.

Clinical Effects of Immuno-Oncology Therapy on Glioblastoma Patients: A Systematic Review.

The most prevalent and deadly primary malignant glioma in adults is glioblastoma (GBM), which has a median survival time of about 15 months. Despite the standard of care for glioblastoma, which includes gross total resection, high-dose radiation, and temozolomide chemotherapy, this tumor is still one of the most aggressive and difficult to treat. So, it is critical to find more potent therapies that can help glioblastoma patients have better clinical outcomes. Additionally, the prognosis for recurring malignant gliomas is poor, necessitating the need for innovative therapeutics. Immunotherapy is a rather new treatment for glioblastoma and its effects are not well studied when it is combined with standard chemoradiation therapy. We conducted this study to evaluate different glioblastoma immunotherapy approaches in terms of feasibility, efficacy, and safety. We conducted a computer-assisted literature search of electronic databases for essays that are unique, involve either prospective or retrospective research, and are entirely written and published in English. We examined both observational data and randomized clinical trials. Eighteen studies met the criteria for inclusion. In conclusion, combining immunotherapy with radiochemotherapy and tumor removal is generally possible and safe, and rather effective in the prolongation of survival measures.

Linac-based stereotactic salvage reirradiation for intraprostatic prostate cancer recurrence: toxicity and outcomes.

BACKGROUND: The rates of local failure after curative radiotherapy for prostate cancer (PC) remain high despite more accurate locoregional treatments available, with one third of patients experiencing biochemical failure and clinical relapse occurring in 30-47% of cases. Today, androgen deprivation therapy (ADT) is the treatment of choice in this setting, but with not negligible toxicity and low effects on local disease. Therefore, the treatment of intraprostatic PC recurrence represents a challenge for radiation oncologists. Prostate reirradiation (Re-I) might be a therapeutic possibility. We present our series of patients treated with salvage stereotactic Re­I for intraprostatic recurrence of PC after radical radiotherapy, with the aim of evaluating feasibility and safety of linac-based prostate Re­I. MATERIALS AND METHODS: We retrospectively evaluated toxicities and outcomes of patients who underwent salvage reirradiation using volumetric modulated arc therapy (VMAT) for intraprostatic PC recurrence. Inclusion criteria were age ≥ 18 years, histologically proven diagnosis of PC, salvage Re­I for intraprostatic recurrence after primary radiotherapy for PC with curative intent, concurrent/adjuvant ADT with stereotactic body radiation therapy (SBRT) allowed, performance status ECOG 0-2, restaging choline/PSMA-PET/TC and prostate MRI after biochemical recurrence, and signed informed consent. RESULTS: From January 2019 to April 2022, 20 patients were recruited. Median follow-up was 26.7 months (range 7-50). After SBRT, no patients were lost at follow-up and all are still alive. One- and 2­year progression free survival (PFS) was 100% and 81.5%, respectively, while 2­year biochemical progression-free survival (bFFS) was 88.9%. Four patients (20%) experienced locoregional lymph node progression and were treated with a further course of SBRT. Prostate reirradiation allowed the ADT start to be postponed for 12-39 months. Re­I was well tolerated by all patients and none discontinued the treatment. No cases of ≥ G3 genitourinary (GU) or gastrointestinal (GI) toxicity were reported. Seven (35%) and 2 (10%) patients experienced acute G1 and G2 GU toxicity, respectively. Late GU toxicity was recorded in 10 (50%) patients, including 8 (40%) G1 and 2 (10%) G2. ADT-related side effects were found in 7 patients (hot flashes and asthenia). CONCLUSION: Linac-based SBRT is a safe technique for performing Re­I for intraprostatic recurrence after primary curative radiotherapy for PC. Future prospective, randomized studies are desirable to better understand the effectiveness of reirradiation and the still open questions in this field.

Histiocytic Sarcoma Involving Cervical Vertebra: A Case Report and Review of the Literature.

Histiocytic sarcoma (HS) is a rare neoplasm composed of cells with immunohistochemical characteristics of mature histiocytes. It can be disseminated or localized and usually involves the skin, spleen, and gastrointestinal tract. Primary involvement of the vertebral column is extremely rare. We report a 29-year-old female who presented with neck pain and had a destructive 35*43*48 mm lesion in C2 with a paravertebral extension. The initial biopsy did not lead to the correct diagnosis. She later developed dysphagia, and the anterior approach was used for tumor decompression. The diagnosis of cervical histiocytic sarcoma was made, and she underwent radiotherapy. The follow-up MRI showed a marked response to radiotherapy. Here, we report the first case of cervical HS, review all cases of vertebral HS, compare patients' characteristics and clinical courses, and discuss diagnostic nuances and treatment options.

Stereotactic Body Radiation Therapy (SBRT) for Oligorecurrent/Oligoprogressive Mediastinal and Hilar Lymph Node Metastasis: A Systematic Review.

INTRODUCTION: Mediastinal or hilar lymph node metastases are a challenging condition in patients affected by solid tumors. Stereotactic body radiation therapy (SBRT) could play a crucial role in the therapeutic management and in the so-called "no-fly zone", delivering high doses of radiation in relatively few treatment fractions with excellent sparing of healthy surrounding tissues and low toxicity. The aim of this systematic review is to evaluate the feasibility and tolerability of SBRT in the treatment of mediastinal and hilar lesions with particular regard to the radiotherapy doses, dose constraints for organs at risk, and clinical outcomes. MATERIALS AND METHODS: Two blinded investigators performed a critical review of the Medline, Web of Knowledge, Google Scholar, Scopus, and Cochrane databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA), starting from a specific question: What is the clinical impact of SBRT for the treatment of oligorecurrent/oligoprogressive mediastinal and hilar metastasis? All retrospective and prospective clinical trials published in English up to February 2022 were analyzed. RESULTS: A total of 552 articles were identified and 12 of them were selected with a total number of 478 patients treated with SBRT for mediastinal or hilar node recurrence. All the studies are retrospective, published between 2015 and 2021 with a median follow-up ranging from 12 to 42.2 months. Studies following SBRT for lung lesions or retreatments after thorax radiotherapy for stage III lung cancer were also included. The studies showed extensive heterogeneity in terms of patient and treatment characteristics. Non-small cell lung cancer was the most frequently reported histology. Different dose schemes were used, with a higher prevalence of 4-8 Gy in 5 or 6 fractions, but dose escalation was also used up to 52 Gy in 4 fractions with dose constraints mainly derived from RTOG 0813 trial. The radiotherapy technique most frequently used was volumetric modulated arc therapy (VMAT) with a median PTV volume ranging from 7 to 25.7 cc. The clinical outcome seems to be very encouraging with 1-year local control (LC), overall survival (OS) and progression-free survival (PFS) rates ranging from 84 to 94%, 53 to 88% and 23 to 53.9%, respectively. Half of the studies did not report toxicity greater than G3 and only five cases of fatal toxicity were reported. CONCLUSIONS: From the present review, it is not possible to draw definitive conclusions because of the heterogeneity of the studies analyzed. However, SBRT appears to be a safe and effective option in the treatment of mediastinal and hilar lymph node recurrence, with a good toxicity profile. Its use in clinical practice is still limited, and there is extensive heterogeneity in patient selection and fractionation schedules. Good performance status, small PTV volume, absence of previous thoracic irradiation, and administration of a high biologically effective dose (BED) seem to be factors that correlate with greater local control and better survival rates. In the presence of symptoms related to the thoracic lymph nodes, SBRT determines a rapid control that lasts over time. We look forward to the prospective studies that are underway for definitive conclusions.

State of the Art in Combination Immuno/Radiotherapy for Brain Metastases: Systematic Review and Meta-Analysis.

OBJECTIVES: Common origins for brain metastases (BMs) are melanoma, lung, breast, and renal cell cancers. BMs account for a large share of morbidity and mortality caused by these cancers. The advent of new immunotherapeutic treatments has made a revolution in the treatment of cancer patients and particularly, as a new concept, if it is combined with radiotherapy, may lead to considerably longer survival. This systematic review and meta-analysis aimed to evaluate the survival rate and toxicities of such a combination in brain metastases. METHODS: To perform a systematic review of the literature until January 2021 using electronic databases such as PubMed, Cochrane Library, and Embase; the Newcastle-Ottawa Scale was used to evaluate the quality of cohort studies. For data extraction, two reviewers extracted the data blindly and independently. Hazard ratio with 95% confidence interval (CI), fixed-effect model, and inverse-variance method was calculated. The meta-analysis has been evaluated with the statistical software Stata/MP v.16 (The fastest version of Stata). RESULTS: In the first step, 494 studies were selected to review the abstracts, in the second step, the full texts of 86 studies were reviewed. Finally, 28 studies were selected consisting of 1465 patients. The addition of IT to RT in the treatment of brain metastasis from melanoma and non-small-cell lung carcinoma was associated with a 39% reduction in mortality rate and has prolonged overall survival, with an acceptable toxicity profile. The addition of IT to RT compared with RT alone has a hazard ratio of 0.39(95% CI 0.34-0.44). CONCLUSIONS: A combination of immuno/radiotherapy (IR) for the treatment of patients with BMs from melanoma and non-small-cell lung carcinoma has prolonged overall survival and reduced mortality rate, with acceptable toxicity. In terms of timing, RT seems to have the best effect on the result when performed before or simultaneously with immunotherapy.

The Role of Interstitial Brachytherapy for Breast Cancer Treatment: An Overview of Indications, Applications, and Technical Notes.

Breast cancer represents the second leading cause of cancer-related death in the female population, despite continuing advances in treatment options that have significantly accelerated in recent years. Conservative treatments have radically changed the concept of healing, also focusing on the psychological aspect of oncological treatments. In this scenario, radiotherapy plays a key role. Brachytherapy is an extremely versatile radiation technique that can be used in various settings for breast cancer treatment. Although it is invasive, technically complex, and requires a long learning curve, the dosimetric advantages and sparing of organs at risk are unequivocal. Literature data support muticatheter interstitial brachytherapy as the only method with strong scientific evidence to perform partial breast irradiation and reirradiation after previous conservative surgery and external beam radiotherapy, with longer follow-up than new, emerging radiation techniques, whose effectiveness is proven by over 20 years of experience. The aim of our work is to provide a comprehensive view of the use of interstitial brachytherapy to perform breast lumpectomy boost, breast-conserving accelerated partial breast irradiation, and salvage reirradiation for ipsilateral breast recurrence, with particular focus on the implant description, limits, and advantages of the technique.

Adenoid Cystic Carcinoma/Basal Cell Carcinoma of the Prostate: Overview and Update on Rare Prostate Cancer Subtypes.

Adenoid cystic carcinoma/basaloid cell carcinoma of the prostate (ACC/BCC) is a very rare variant of prostate cancer with uncertain behavior. Few cases are reported in the literature. Data on treatment options are scarce. The aim of our work was to retrospectively review the published reports. Thirty-three case reports or case series were analyzed (106 patients in total). Pathological features, management, and follow-up information were evaluated. Despite the relatively low level of evidence given the unavoidable lack of prospective trials for such a rare prostate tumor, the following considerations were made: prostate ACC/BCC is an aggressive tumor often presenting with locally advanced disease and incidental diagnosis occurs during transurethral resection of the prostate for urinary obstructive symptoms. Prostate-specific antigen was not a reliable marker for diagnosis nor follow-up. Adequate staging with Computed Tomography (CT) scan and Magnetic Resonance Imaging (MRI) should be performed before treatment and during follow-up, while there is no evidence for the use of Positron Emission Tomography (PET). Radical surgery with negative margins and possibly adjuvant radiotherapy appear to be the treatments of choice. The response to androgen deprivation therapy was poor. Currently, there is no evidence of the use of truly effective systemic therapies.

Delayed Effect of Dendritic Cells Vaccination on Survival in Glioblastoma: A Systematic Review and Meta-Analysis.

BACKGROUND: Dendritic cell vaccination (DCV) strategies, thanks to a complex immune response, may flare tumor regression and improve patients' long-term survival. This meta-analysis aims to assess the efficacy of DCV for newly diagnosed glioblastoma patients in clinical trials. METHODS: The study databases, including PubMed, Web of Knowledge, Google Scholar, Scopus, and Cochrane, were searched by two blinded investigators considering eligible studies based on the following keywords: "glioblastoma multiforme", "dendritic cell", "vaccination", "immunotherapy", "immune system", "immune response", "chemotherapy", "recurrence", and "temozolomide". Among the 157 screened, only 15 articles were eligible for the final analysis. RESULTS: Regimens including DCV showed no effect on 6-month progression-free survival (PFS, HR = 1.385, 95% CI: 0.822-2.335, p = 0.673) or on 6-month overall survival (OS, HR = 1.408, 95% CI: 0.882-2.248, p = 0.754). In contrast, DCV led to significantly longer 1-year OS (HR = 1.936, 95% CI: 1.396-2.85, p = 0.001) and longer 2-year OS (HR = 3.670, 95% CI: 2.291-5.879, p = 0.001) versus control groups. Hence, introducing DCV could lead to increased 1 and 2-year survival of patients by 1.9 and 3.6 times, respectively. CONCLUSION: Antitumor regimens including DCV can effectively improve mid-term survival in patients suffering glioblastoma multiforme (GBM), but its impact emerges only after one year from vaccination. These data indicate the need for more time to achieve an anti-GBM immune response and suggest additional therapeutics, such as checkpoint inhibitors, to empower an earlier DCV action in patients affected by a very poor prognosis.

Prognostic factors, efficacy, and toxicity of involved-node stereotactic body radiation therapy for lymph node oligorecurrent prostate cancer : An investigation of 117 pelvic lymph nodes.

BACKGROUND: The optimal radiotherapy regimen is not yet defined in the setting of oligorecurrent prostate cancer (oligorPC). There is evidence of high variability in treatment protocols among different centers worldwide, and no international consensus guidelines on treatment volumes, radiation schedules, and techniques. The purpose of the present retrospective study is to evaluate the efficacy and safety of involved-pelvic-node stereotactic body radiotherapy (SBRT) for oligorPC. MATERIALS AND METHODS: Patients with pelvic node oligorPC following primary surgery, radical radiotherapy, or salvage radiotherapy for biochemical or local relapse of prostate cancer who underwent involved-node SBRT with biological effective dose (BED) > 100 Gy, with or without concurrent and adjuvant androgen deprivation therapy (ADT), were retrospectively evaluated. Biochemical progression-free survival (bPFS), distant progression-free survival (DPFS), overall survival (OS), possible prognostic factors, and toxicity outcomes were investigated. RESULTS: From November 2012 to December 2019, 74 patients fitted the selection criteria. A total of 117 lesions were treated. Median follow-up was 31 months (range 6-89). Concurrent ADT was administered in 58.1% of patients. The 1­year, 2­year, and 3­year DPFS was 77%, 37%, and 19%, respectively; the 1­year, 2­year, and 3­year OS was 98%, 98%, and 95%, respectively. The presence of a single target lesion was associated with a statistically significant impact on OS. No in-field recurrence occurred. Patients who reached early prostate-specific antigen (PSA) nadir (< 3 months after SBRT) had a lower 3­year survival (p = 0.004). The value of PSA nadir after SBRT and the time between primary treatment and SBRT had an impact on bPFS. Concomitant ADT was associated with improved DPFS. No acute or early late (> 6 months) genitourinary and gastrointestinal adverse events of any grade were reported, albeit with relatively short median follow-up. CONCLUSION: SBRT is a safe and effective treatment for oligorPC, with a 100% local control rate in our series. It is not possible to clearly assess the opportunity to postpone ADT prescription in patients with two or more nodal metastases. The number of secondary lesions, time-to-nadir PSA, PSA nadir value, and the time interval between primary treatment and SBRT were identified as prognostic factors. Future prospective randomized studies are desirable to better understand the still open questions regarding the oligorecurrent prostate cancer state.

Ductal prostate cancer: Clinical features and outcomes from a multicenter retrospective analysis and overview of the current literature.

Objective: The aim of the study is to evaluate clinical features and outcomes after different therapeutic strategies for ductal prostate adenocarcinoma (DPC), a rare but aggressive subtype of invasive prostate cancer (PCa) accounting for, in the pure and mixed form, 1% or less and 5% or less, respectively, of all the newly diagnosed PCa. Materials and methods: Patients with a proven diagnosis of DPC undergoing surgery, radiotherapy, and androgen deprivation therapy, alone or in combination, were considered for this multicenter, retrospective study. The study assessed overall survival (OS), disease-free survival (DFS), and age-related disease-specific survival. Results: Eighty-one patients met the study inclusion criteria. Pure DPC was found in 29 patients (36%) and mixed ductal-acinar-PCa in 52 patients (64%). After a median follow-up of 63 months (range, 3-206 months), 3- and 5-year OS rates were 84% and 67%, respectively, and 3- and 5-year DFS rates were 54% and 34%, respectively. There were no significant differences in OS or DFS between the pure and mixed DPC groups. Pure DPC was associated with a higher rate of metastatic disease at onset. Patients 74 years or younger had better disease-specific survival (p=0.0019). A subgroup analysis favored radiotherapy as the primary treatment for nonmetastatic, organ-confined DPC (3- and 5-year DFS of 80% and 50%, respectively, compared with 5-year DFS of 35% for surgical patients; p = 0.023). Conclusions: Our study found DPC to be rarer, more aggressive, more likely to metastasize, and have a worse prognosis than the common acinar variant, especially in its pure form. Multicenter series are encouraged to obtain large data sets, or propensity score matching analyses with patients with conventional PCa are desirable to understand the best therapeutic approach and improve outcomes.

Radiation-induced breast angiosarcoma: report of two patients after accelerated partial breast irradiation (APBI) and review of the literature.

BACKGROUND: Angiosarcoma may rarely complicate radiotherapy of breast cancer. This so-called radiation-induced angiosarcoma (RIAS) occurs in less than 0.3% of patients that underwent breast conservation surgeries, usually years after completion of radiotherapy. CASE PRESENTATION: we introduce two cases of invasive ductal carcinoma who underwent lumpectomy and accelerated partial breast irradiation (APBI) as an alternative protocol to whole breast irradiation (WBI). They received adjuvant partial breast radiotherapy on tumor cavity for a total dose of 38.5 Gy in 10 fractions in 5 days using 3D-external-beam RT. In both cases, RIAS occurred eight years after radiotherapy, in the sub-cicatricial area in one patient and outside the irradiated area in the other one. They both underwent radical surgery and chemotherapy was performed in one patient. DISCUSSION: The underlying mechanism for development of RIAS is not well known, but its incidence seems to be increasing. RIAS after partial breast irradiation is very rare and has been reported in two cases so far. As it may be suggested in case 2, it is still a matter of debate if the risk of radiation-induced sarcoma is radiation-dose dependent. Although mastectomy is considered as a standard treatment, choice of treatment should be made according to the patient's specifications. CONCLUSION: There are very few studies in the literature that report RIAS after APBI. Present study is the only one reporting two cases after the external 3D technique APBI. Prognosis of RIAS remains poor. Only a careful evaluation in a multidisciplinary context can offer to the patients the best result in terms of local control and survival.

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.

Adjunctive treatment of myxopapillary ependymoma.

Myxopapillary ependymoma are rare tumors and optimal therapeutic strategy is remained controversial. The main treatments for myxopapillary ependymoma tumors include surgery and radiotherapy. Hence, the present study aimed to review adjuvant treatment of myxopapillary ependymoma, focusing on spinal myxopapillary ependymoma. The information sources of all articles were the English authoritative databases including PubMed, Web of science, Scopus, Science direct and Google scholar. In this review study, the keywords including adjuvant, treatment, myxopapillary and ependymoma were selected from MeSH medical library. Related articles were published from 2000 to 2020. Given radiation tolerance in the spinal cord is 10-15% lower than that of the brain, it also should be noted that with increased dose and scope of therapeutic field, the corresponding risks are increased, as well. Also, chemotherapy has never been used as the primary treatment approach. Radiotherapy's value is considered while involving with sensitive areas where chemotherapy is also recommended. Gross total resection is the preferred primary treatment. But the role of adjuvant radiotherapy is debated in different tumor and patient scenarios and no standard treatment strategy had been defined yet. The bottom line is that as long as cellular and molecular methods or gene therapy can be used in the treatment of myxopapillary ependymoma, all the studies confirm that the best treatment method is still wide surgical resection as much as possible.

Caesarean Section vs. Normal Vaginal Delivery: A Game Theory Discussion in Reimbursement Interventions.

BACKGROUND: The rate of caesarean section (C-section) in Iran is too high, so having a plan to control it is crucial. Since one of the most important reasons for inclination of providers to do C-section is financial issues, the purpose of this study was offering financial solutions for increasing normal vaginal delivery (NVD) and decreasing non-indicated C-section. METHODS: This analytical-descriptive research, used game theory for offering financial mechanisms. The game was a dynamic one in which the backward induction was used to obtain a Nash equilibrium. Financial structure and the mean number of NVD and C-section in a certain period of time in comparison with standards were as the main influential factors on financial dimensions and were included in the model. RESULTS: The effect of financial structure was shown through a specified insurance for childbirth, existence of a monitoring department and tariffs. CONCLUSION: The main solution for controlling C-section in designed game was taxes and fines for physician or hospital in non- indicated cases and giving reward otherwise.

Primary Cutaneous Lymphoma-Associated Pseudoepitheliomatous Hyperplasia Masquerading as Squamous Cell Carcinoma in a Young Adult.

Primary cutaneous anaplastic large cell lymphoma is a T-cell malignancy with atypical CD30 positive lymphocytes. Pseudoepitheliomatous hyperplasia is an uncommon finding in primary cutaneous anaplastic large cell lymphoma, and may mimic squamous cell carcinoma as pseudomalignancy. Careful attention of a pathologist to correct diagnosis of pseudoepitheliomatous hyperplasia and its underlying causes will help physicians to avoid inappropriate management. Here, we present a 22-year-old man referred to our hospital with a solitary nodule persistent on his forearm which was diagnosed as squamous cell carcinoma in the first biopsy. The lesion recurred after two months and histopathologic and immunohistochemistry examination revealed anaplastic large cell lymphoma with florid pseudoepitheliomatous hyperplasia which masquerading as well-differentiated squamous cell carcinoma. Diagnosis of pseudoepitheliomatous hyperplasia must guide the pathologist to search for underlying causes, such as primary cutaneous lymphoma. Pseudoepitheliomatous hyperplasia may mimic squamous cell carcinoma and this can result in inappropriate diagnosis and management.

Gastrointestinal adverse effects of antiepileptic drugs in intractable epileptic patients.

Gastrointestinal (GI) discomforts are among the most common side effects of antiepileptic drugs (AEDs) that might lead to discontinuation or irregular consumption of the drugs. This study was conducted to evaluate the frequency of GI side effects of different AEDs in intractable epileptic patients treated with single or multiple drugs. GI discomfort of 100 epileptic patients (aged 35-76 years) treated with one or multiple AEDs was assessed. Seventy six patients (76%) were treated with two or more AEDs, and 24 (24%) were on monotherapy. The most common prescribed drug for monotherapy was carbamazepine and the most frequent combination was phenytoin and carbamazepine. Patients were suffering from different GI side effects including heartburn (34.6%), nausea (33.7%), constipation (26%), vomiting (22.1%), diarrhea (21.2%) and dysphagia (19.2%). Nausea and vomiting were significantly higher in patients receiving monotherapy with carbamazepine and valproic acid, respectively. When phenytoin, gabapentine, or valproic acid was added to the other AEDs, the risk of the occurrence of diarrhea, dysphagia, or heartburn was significantly increased, respectively. Addition of gabapentine to the other AEDs in multiple drug therapy was accompanied with the highest frequency of GI complications. This study indicated that GI side effects, which can affect drug absorption and utilization, were common in intractable epileptic patients with long-term AEDs treatment. This may influence the efficacy of the therapy with AEDs and enhance the probability of further attacks.