PErspective and current status of Radiotherapy Service in IRan (PERSIR)-1 study: assessment of current external beam radiotherapy facilities, staff and techniques compared to the international guidelines.

BACKGROUND AND PURPOSE: Radiotherapy (RT) is an essential treatment modality against cancer and becoming even more in demand due to the anticipated increase in cancer incidence. Due to the rapid development of RT technologies amid financial challenges, we aimed to assess the available RT facilities and the issues with achieving health equity based on current equipment compared to the previous reports from Iran. MATERIALS AND METHODS: A survey arranged by the Iran Cancer Institute's Radiation Oncology Research Center (RORC) was sent to all of the country's radiotherapy centers in 2022. Four components were retrieved: the reimbursement type, equipment, human resources, and patient load. To calculate the radiotherapy utilization rate (RUR), the Lancet Commission was used. The findings were compared with the previous national data. RESULTS: Seventy-six active radiotherapy centers with 123 Linear accelerators (LINACs) were identified. The centers have been directed in three ways. 10 (20 LINACs), 36 (50 LINACs), and 30 centers (53 LINACs) were charity-, private-, and public-based, respectively. Four provinces had no centers. There was no active intraoperative radiotherapy machine despite its availability in 4 centers. One orthovoltage X-ray machine was active and 14 brachytherapy devices were treating patients. There were 344, 252, and 419 active radiation oncologists, medical physicists, and radiation therapy technologists, respectively. The ratio of LINAC and radiation oncologists to one million populations was 1.68 and 4.10, respectively. Since 2017, 35±5 radiation oncology residents have been trained each year. CONCLUSION: There has been a notable growth in RT facilities since the previous reports and Iran's situation is currently acceptable among LMICs. However, there is an urgent need to improve the distribution of the RT infrastructure and provide more facilities that can deliver advanced techniques.

Update on immune-based therapy strategies targeting cancer stem cells.

Accumulating data reveals that tumors possess a specialized subset of cancer cells named cancer stem cells (CSCs), responsible for metastasis and recurrence of malignancies, with various properties such as self-renewal, heterogenicity, and capacity for drug resistance. Some signaling pathways or processes like Notch, epithelial to mesenchymal transition (EMT), Hedgehog (Hh), and Wnt, as well as CSCs' surface markers such as CD44, CD123, CD133, and epithelial cell adhesion molecule (EpCAM) have pivotal roles in acquiring CSCs properties. Therefore, targeting CSC-related signaling pathways and surface markers might effectively eradicate tumors and pave the way for cancer survival. Since current treatments such as chemotherapy and radiation therapy cannot eradicate all of the CSCs and tumor relapse may happen following temporary recovery, improving novel and more efficient therapeutic options to combine with current treatments is required. Immunotherapy strategies are the new therapeutic modalities with promising results in targeting CSCs. Here, we review the targeting of CSCs by immunotherapy strategies such as dendritic cell (DC) vaccines, chimeric antigen receptors (CAR)-engineered immune cells, natural killer-cell (NK-cell) therapy, monoclonal antibodies (mAbs), checkpoint inhibitors, and the use of oncolytic viruses (OVs) in pre-clinical and clinical studies. This review will mainly focus on blood malignancies but also describe solid cancers.

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.

Implications for pelvic lymph node irradiation in definitive chemoradiotherapy of node negative muscle invasive bladder cancer based on predictive factors of clinicopathologic discrepancy.

PURPOSE: To identify pre-surgical imaging predictive value and factors associated with the clinicopathologic discrepancy for implication of definitive pelvic radiotherapy in clinically node-negative bladder cancer. METHOD: The documented data of bladder cancer patients who underwent radical cystectomy plus pelvic lymphadenectomy were collected retrospectively. Patients' characteristics, last imaging, pathology reports, disease-specific survival and overall survival were retrieved. RESULTS: From 142 patients, pre-surgical imaging had a sensitivity of 76.4%, specificity of 73.7%, positive predictive value (PPV) of 94.9%, and negative predictive value (NPV) of 32.6% (p value < 0.0001) for detection of muscle invasion. Also, for detection of positive lymph nodes, imaging had a sensitivity of 31.8%, specificity of 85.7%, PPV of 50%, and NPV of 73.7% (p value: 0.022). 44.4% of study population were upstaged after surgery (24.6% associated with N-upstaging) and 18.3% were downstaged (12% associated with N-downstaging). Receipt of neoadjuvant chemotherapy and T-stage were not correlated with N-upstaging. On multivariate analysis, lymphovascular invasion (LVI) maintained its significance for independent prediction of upstaging (OR 3.3, 95% CI 1.5-7.5, p value: 0.004) and inversely with downstaging (OR 0.34, 95% CI 0.12-0.96, p value: 0.04). Older age (OR 1.03, 95% CI 1.0-1.05, p value 0.047), positive margins (OR 2.1, 95% CI 1.2-3.8, p value 0.011), presence of LVI (OR 2.5, 95% CI 1.4-4.7, p value 0.003), perineural invasion (OR 2.0, 95% CI 1.2-3.4, p value 0.013), and lymph node ratio (OR 1.011, 95% CI 1.001-1.021, p value 0.03) were associated with worse survival. Also, N-upstaging independently predicted a worse survival after controlling for surgical pathology stage (OR 2.3, 95% CI 1.2-4.5, p value 0.011). CONCLUSIONS: The optimal target volume in definitive chemoradiotherapy of node-negative bladder cancer patients remains to be established. Since then, customizing the treatment is considered especially for positive LVI in TURBT specimen.

Assessment of Tolerability, Response and Complications of Concurrent Chemoradiation With Capecitabine and Cisplatin in Muscle-Invasive Bladder Cancer; A Single Arm Study.

PURPOSE: To evaluate the feasibility, tolerance and efficacy of cisplatin+capecitabine as a proposed combination in concurrent chemoradiotherapy for patients with muscle-invasive bladder cancer (MIBC). METHODS: MIBC patients with stage T2-T4aN0M0 participated in this single-arm clinical trial. After maximal TURBT, 66Gy/33 daily fractions of radiation were administered with concurrent chemotherapy of cisplatin (35 mg/m2) and capecitabine (625 mg/m2). The primary endpoint was treatment tolerability, defined as receiving capecitabine+cisplatin combination for at least 5 weeks during radiation therapy. The secondary endpoints included complete response (CR) and acute toxicity rates. RESULTS: This study included 19 MIBC patients from 2018 to 2019. Eighteen patients (94.7%, 95%CI: 75.4-99.0) completed the planned treatment course. Only one patient (5.26%, 95%CI: 0.9-24.6) discontinued the treatment due to grade-3 GI toxicity. Among those who completed the treatment, CR was seen in 12 patients (66.7%, 95% CI = 44.4-88.9) with no grade ≥ 3 toxicities. The most common grade-2 side effects during therapy were renal complications (57.9%), and the only grade-2 complication after therapy was urinary-related (11.1%). The median follow-up was 31 months and the median overall survival (OS) was 31 months. The 2-year OS was 78% (95% CI 58.4-97.6), Cystectomy-free survival was 61% (95% CI: 37.5-84.5), and the median OS after recurrence was 13 months. Distant metastases were the first type of recurrence in most patients with a recurrence, which occurred in 7 (36.8%) patients. Median metastasis-free survival (MFS) was 30 months, and 2-year MFS was 66% (95% CI:45-87). CONCLUSION: The promising tolerability rate seen with concurrent cisplatin+capecitabine in this study was comparable to the available literature. Thus, this combination concurrently with radiation warrants further studies in the context of chemoradiotherapy of MIBC.

Evaluation of Survival Rate and Associated Factors in Patients with Cervical Cancer: A Retrospective Cohort Study.

BACKGROUND: Cervical cancer, the most common gynecological cancer, is a matter of concern, especially in developing countries. The present study investigates survival rates, associated factors, and post-treatment follow-up status in cervical cancer patients. STUDY DESIGN: A retrospective cohort study. METHODS: This study was conducted on 187 patients referred to an academic referral cancer center in Iran from 2014-2020. Overall survival (OS) and event-free survival (EFS) were evaluated using Kaplan Meyer analysis. The event was defined as recurrence, metastasis, or death. RESULTS: The patients came for post-treatment visits for a median of 36 months (interquartile range [IQR]: 18-51). The median OS and EFS were 24 and 18 months, respectively. The 1- and 3- year OS rates were 90% and 72%, respectively. The 1- and 3- year EFS rates were 76% and 61%, respectively. Stage ≥ III (hazard ratio [HR]: 3.1, 95% confidence interval [CI]: 1.5, 6.5, P < 0.001) and tumor size > 4 cm (HR: 2.5, 95% CI: 1.2, 4.9, P = 0.006) predicted lower OS. The most common histopathology was squamous cell carcinoma (SCC) (71.1%) with non-significant higher 3- year OS (HR: 0.62, 95% CI: 0.33, 1.16, P = 0.13). No significant difference in OS was found between adjuvant and definitive radiotherapy in both early and advance-staged patients (Log-rank = 0.7 P = 0.4, log-rank = 1.6, P = 0.2, respectively). CONCLUSION: As evidenced by the obtained results, the survival of patients was lower compared to that in developed countries. Higher stage and tumor size led to shorter survival. The histopathology and type of treatment in comparable stages did not have any significant impact on survival.

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.