Evaluating the Effectiveness of Proton Beam Therapy Compared to Conventional Radiotherapy in Non-Metastatic Rectal Cancer: A Systematic Review of Clinical Outcomes.

Background and Objectives: Conventional radiotherapies used in the current management of rectal cancer commonly cause iatrogenic radiotoxicity. Proton beam therapy has emerged as an alternative to conventional radiotherapy with the aim of improving tumour control and reducing off-set radiation exposure to surrounding tissue. However, the real-world treatment and oncological outcomes associated with the use of proton beam therapy in rectal cancer remain poorly characterised. This systematic review seeks to evaluate the radiation dosages and safety of proton beam therapy compared to conventional radiotherapy in patients with non-metastatic rectal cancer. Materials and Methods: A computer-assisted search was performed on the Medline, Embase and Cochrane Central databases. Studies that evaluated the adverse effects and oncological outcomes of proton beam therapy and conventional radiotherapy in adult patients with non-metastatic rectal cancer were included. Results: Eight studies were included in this review. There was insufficient evidence to determine the adverse treatment outcomes of proton beam therapy versus conventional radiotherapy. No current studies assessed radiotoxicities nor oncological outcomes. Pooled dosimetric comparisons between proton beam therapy and various conventional radiotherapies were associated with reduced radiation exposure to the pelvis, bowel and bladder. Conclusions: This systematic review demonstrates a significant paucity of evidence in the current literature surrounding adverse effects and oncological outcomes related to proton beam therapy compared to conventional radiotherapy for non-metastatic rectal cancer. Pooled analyses of dosimetric studies highlight greater predicted radiation-sparing effects with proton beam therapy in this setting. This evidence, however, is based on evidence at a moderate risk of bias and clinical heterogeneity. Overall, more robust, prospective clinical trials are required.

Focused versus conventional radiotherapy in spinal oncology: is there any difference in fusion rates and pseudoarthrosis?

INTRODUCTION: Radiotherapy is considered standard of care for adjuvant peri-operative treatment of many spinal tumors, including those with instrumented fusion. Unfortunately, radiation treatment has been linked to increased risk of pseudoarthrosis. Newer focused radiotherapy strategies with enhanced conformality could offer improved fusion rates for these patients, but this has not been confirmed. METHODS: We performed a retrospective analysis of patients at three tertiary care academic institutions with primary and secondary spinal malignancies that underwent resection, instrumented fusion, and peri-operative radiotherapy. Two board certified neuro-radiologists used the Lenke fusion score to grade fusion status at 6 and 12-months after surgery. Secondary outcomes included clinical pseudoarthrosis, wound complications, the effect of radiation timing and radiobiological dose delivered, the use of photons versus protons, tumor type, tumor location, and use of autograft on fusion outcomes. RESULTS: After review of 1252 spinal tumor patients, there were 60 patients with at least 6 months follow-up that were included in our analyses. Twenty-five of these patients received focused radiotherapy, 20 patients received conventional radiotherapy, and 15 patients were treated with protons. There was no significant difference between the groups for covariates such as smoking status, obesity, diabetes, intraoperative use of autograft, and use of peri-operative chemotherapy. There was a significantly higher rate of fusion for patients treated with focused radiotherapy compared to those treated with conventional radiotherapy at 6-months (64.0% versus 30.0%, Odds ratio: 4.15, p = 0.036) and 12-months (80.0% versus 42.1%, OR: 5.50, p = 0.022). There was a significantly higher rate of clinical pseudoarthrosis in the conventional radiotherapy cohort compared to patients in the focused radiotherapy cohort (19.1% versus 0%, p = 0.037). There was no difference in fusion outcomes for any of the secondary outcomes except for use of autograft. The use of intra-operative autograft was associated with an improved fusion at 12-months (66.7% versus 37.5%, OR: 3.33, p = 0.043). CONCLUSION: Focused radiotherapy may be associated with an improved rate of fusion and clinical pseudoarthrosis when compared to conventional radiation delivery strategies in patients with spinal tumors. Use of autograft at the time of surgery may be associated with improved 12-month fusion rates. Further large-scale prospective and randomized controlled studies are needed to better stratify the effects of radiation delivery modality in these patients.

Radiobiological and Treatment-Related Aspects of Spatially Fractionated Radiotherapy.

The continuously evolving field of radiotherapy aims to devise and implement techniques that allow for greater tumour control and better sparing of critical organs. Investigations into the complexity of tumour radiobiology confirmed the high heterogeneity of tumours as being responsible for the often poor treatment outcome. Hypoxic subvolumes, a subpopulation of cancer stem cells, as well as the inherent or acquired radioresistance define tumour aggressiveness and metastatic potential, which remain a therapeutic challenge. Non-conventional irradiation techniques, such as spatially fractionated radiotherapy, have been developed to tackle some of these challenges and to offer a high therapeutic index when treating radioresistant tumours. The goal of this article was to highlight the current knowledge on the molecular and radiobiological mechanisms behind spatially fractionated radiotherapy and to present the up-to-date preclinical and clinical evidence towards the therapeutic potential of this technique involving both photon and proton beams.

Modality of Radiotherapy and Overall Survival in Pediatric Diffuse Brainstem Gliomas: Implications for Resource-Constrained Settings.

BACKGROUND: Childhood diffuse brainstem glioma (dBSG) is a rare tumor with a poor prognosis. Any tumor-directed surgical intervention is difficult. Magnetic resonance imaging forms the mainstay of diagnosis and radiation therapy has remained the backbone of therapy. In this study, we compare the outcomes of conformal radiotherapy with conventional therapy in the context of resource-constrained settings. METHODS: In this retrospective analysis, conducted between 2010 and 2019, all pediatric patients with a diagnosis of dBSG were analyzed. The survival data were calculated in months from the date of diagnosis. Survival differences between variables were compared using the Log-rank test and the risk of death was calculated using Cox regression analysis. RESULTS: A total of 20 patients (11 males, 55%) with a diagnosis of dBSG were included. Median age at diagnosis was 6.5 years. No surgical resection or biopsy was done in any patient. Fifteen (75%) patients received radiotherapy and only 4 (20%) patients received additional chemotherapy. Five (25%) patients did not receive any form of anti-cancer therapy. Median overall survival (OS) was 8 months (95% CI 5.2-10.8). Females were at a higher risk of death than males. Children treated with radiotherapy had a longer OS than untreated children; however, the modality of radiotherapy employed or the addition of chemotherapy did not affect the OS. CONCLUSION: Radiotherapy, irrespective of the modality, increases the survival of children with dBSG in resource-poor settings. Additionally, socioeconomic concerns need to be addressed in the management of these tumors, especially in the case of female children. Lay summaryChildhood diffuse brainstem glioma (dBSG) is a rare tumor with a poor prognosis. Any tumor-directed surgical intervention is difficult. Magnetic resonance imaging forms the mainstay of diagnosis and radiation therapy has remained the backbone of therapy. In this 10-year retrospective study, we compare the outcomes of conformal radiotherapy with conventional therapy in the context of resource-constrained settings. A total of 20 patients with a diagnosis of dBSG were included with a median age at diagnosis of 6.5 years (5.25-8.75). No surgical resection or biopsy was done in any patient. Fifteen (75%) patients received radiotherapy and only 4 (20%) patients received additional chemotherapy. Five (25%) patients did not receive any form of anti-cancer therapy. Median overall survival (OS) was 8 months (95% CI 5.2-10.8). Females were at a 3.4-fold (95% CI 1.0-12.1) higher risk of death than males. Children treated with radiotherapy had a longer OS than untreated children; however, the modality of radiotherapy employed or the addition of chemotherapy did not affect the OS. Radiotherapy, irrespective of the modality, increases the survival of children with dBSG in resource-poor settings. Additionally, socioeconomic concerns need to be addressed in the management of these tumors, especially in the case of female children.

Hypofractionated radiotherapy versus conventional radiotherapy in patients with intermediate- to high-risk localized prostate cancer: a meta-analysis of randomized controlled trials.

BACKGROUND: Prostate cancer is one of the most common cancers in the world. The results of treatment after hypofractionated radiotherapy only have been reported from several small randomized clinical trials. Therefore, we conducted a meta-analysis to compare clinical outcomes of hypofractionated radiotherapy versus conventional radiotherapy in the treatment of intermediate- to high-risk localized prostate cancer. METHODS: Relevant studies were identified through searching related databases till August 2018. Hazard ratio (HR) or risk ratio (RR) with its corresponding 95% confidence interval (CI) was used as pooled statistics for all analyses. RESULTS: The meta-analysis results showed that overall survival (HR = 1.12, 95% CI: 0.93-1.35, p = 0.219) and prostate cancer-specific survival (HR = 1.29, 95% CI: 0.42-3.95, p = 0.661) were similar in two groups. The pooled data showed that biochemical failure was RR = 0.90, 95% CI: 0.76-1.07, p = 0.248. The incidence of acute adverse gastrointestinal events (grade ≥ 2) was higher in the hypofractionated radiotherapy (RR = 1.70, 95% CI: 1.12-2.56, p = 0.012); conversely, for late grade ≥ 2 gastrointestinal adverse events, a significant increase in the conventional radiotherapy was found (RR = 0.75, 95% CI: 0.61-0.91, p = 0.003). Acute (RR = 1.01, 95% CI: 0.89-1.15, p = 0.894) and late (RR = 0.98, 95% CI: 0.86-1.10, p = 0.692) genitourinary adverse events (grade ≥ 2) were similar for both treatment groups. CONCLUSION: Results suggest that the efficacy and risk for adverse events are comparable for hypofractionated radiotherapy and conventional radiotherapy in the treatment of intermediate- to high-risk localized prostate cancer.

Dose Volume Effect of Acute Diarrhea in Post-Operative Radiation for Gynecologic Cancer.

BACKGROUND: Diarrhea is the primary symptom of concern in acute post-operative radiation-induced enteritis in gynecologic cancer. We retrospectively studied the correlation between the volume of irradiated small bowel and the development of acute diarrhea in these patients. MATERIALS AND METHODS: A total of 100 post-operative gynecologic cancer patients were analyzed. Pelvic computed tomography was performed to calculate the volume of irradiated small bowel. A dose-volume histogram was calculated from 5 to 40 Gy at 5 Gy intervals. Patients receiving conventional whole pelvic radiation therapy (RT) were assigned to Group I, and those who received intensity-modulated RT (IMRT) were assigned to Group II. A total dose of 40-50 Gy was delivered at 1.8-2.0 Gy per fraction daily. Acute diarrhea during treatment was scored. All data were expressed as a mean ± standard deviation. Different dose-volume parameters for small bowel in Grades 0-1 and Grades 2-3 diarrhea were calculated by the independent t-test. Univariate analysis of diarrhea risk factors was performed with the independent t-test or Chi-square/Fisher exact test. RESULTS: Of the 77 patients who received conventional RT, 44 (57.14%) experienced Grades 2-3 toxicities. Of the 23 patients who received IMRT, 9 (39.13%) experienced Grades 2-3 toxicities. Concurrent chemotherapy was slightly associated with a higher damage score in both groups (p = 0.028). None of the patient factors (weight, percentage depth dosage, dose fraction, distance from skin to tumor, lymph node metastasis, chemotherapy, block, brachytherapy, hypertension, or diabetes) were correlated with diarrhea in the two groups. The volumes of irradiated small bowel in patients who experienced Grades 2-3 diarrhea were significantly larger than those in patients who experienced Grades 0-1 diarrhea at all dose levels in Group I. V20 (372.19 ± 133.26 cm3, p = 0.004) was an independent factor for developing Grades 2-3 diarrhea in Group I. V25 (290.35 ± 130.22 cm3, p = 0.001) was an independent risk factor for all patients who developed higher score diarrhea. CONCLUSIONS: The volume of irradiated small bowel was an independent risk factor for all patients who developed diarrhea, especially those undergoing conventional RT.

Comparison of clinical outcomes and toxicity in endometrial cancer patients treated with adjuvant intensity-modulated radiation therapy or conventional radiotherapy.

PURPOSE: To evaluate the treatment outcomes and toxicity in endometrial cancer patients treated with hysterectomy and adjuvant intensity-modulated radiation therapy (IMRT) or conventional radiotherapy (CRT). METHODS: There were 101 patients with stage IA-IIIC2 endometrial carcinoma treated with hysterectomy and adjuvant radiotherapy. In total, 36 patients received adjuvant CRT and 65 were treated with adjuvant IMRT. The endpoints were overall survival, local failure-free survival, and disease-free survival. Patients were assessed for acute toxicity weekly according to the Common Terminology Criteria for Adverse Events version 3.0. Late toxicity was evaluated according to the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Schema. RESULTS: The 5-year overall survival, local failure-free survival, and disease-free survival for the CRT group and the IMRT group were 82.9% versus 93.5% (p = 0.26), 93.7% versus 89.3% (p = 0.68), and 88.0% versus 82.8% (p = 0.83), respectively. Four (11.1%) patients had Grade 3 or greater acute gastrointestinal (GI) toxicity and three (8.3%) patients had Grade 3 or greater acute genitourinary (GU) toxicity in the CRT group, whereas four (6.2%) patients had Grade 3 or greater acute GI toxicity in the IMRT group and no patient had severe GU toxicity. There was one (2.8%) patient who had Grade 3 or greater late GI toxicity and one (2.8%) patient had Grade 3 or greater late GU toxicity in the CRT group, whereas no patient had severe GI or GU toxicity in the IMRT group. CONCLUSION: Adjuvant IMRT for endometrial cancer patients had comparable clinical outcomes with CRT and had less acute and late toxicity.

Tumor volume changes after stereotactic, hypofractionated and conventional radiotherapy in paragangliomas of head and neck.

BACKGROUND: The aim of this study is comparison the effectiveness of stereotactic, hypofractionated and conventional radiotherapy assessed by the tumor volume changes of paraganglioma located in the head and neck region concerning fractional and total doses. METHODS: We analyzed 76 patients after radiotherapy due to paraganglioma who were assigned to 3 groups considering fractional (≤2 Gy, 3-5.5 Gy, ≥6 Gy) and total (≤20 Gy, 21-40 Gy, >40 Gy) doses. The volumes of irradiated tumors were measured and compared based on diagnostic images performed before and after the treatment. RESULTS: The mean tumor volume after the treatment with the lowest fractional dose (≤2 Gy) was decreased by 14.4 cm3. In patients treated with higher fractional doses (>2 Gy), the mean tumor volumes decreased by less than 1 cm3 for hypofractionated and stereotactic radiotherapy. 15.9 cm3 reduction of the mean tumor volume after the treatment with the highest RT total dose (>40 Gy) was stated. In patients treated with total doses ≤20 Gy and 21-40 Gy, the mean tumor volume was stable and reduced by 1.15 cm3, respectively. The analysis demonstrates a statistically significant (p < 0.05) treatment advantage in patients after the lowest fractional and highest total doses. CONCLUSION: The reduction of the tumor's volume was reported after conventional and unconventional radiotherapy. The most significant depletion of the paraganglioma volume was noted after a factional dose ≤2 Gy and a total dose >40 Gy.

Reirradiation of metastases of the central nervous system: part 2-metastatic epidural spinal cord compression.

An increasing number of patients irradiated for metastatic epidural spinal cord compression (MESCC) experience an in-field recurrence and require a second course of radiotherapy. Reirradiation can be performed with conventional radiotherapy or highly-conformal techniques such as intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT), and stereotactic body radiation therapy (SBRT). When using conventional radiotherapy, a cumulative biologically effective dose (BED) ≤120 calculated with an α/ß value of 2 Gy (Gy2) was not associated with radiation myelopathy in a retrospective study of 124 patients and is considered safe. In that study, conventional reirradiation led to improvements of motor deficits in 36% of patients and stopped further symptomatic progression in another 50% (overall response 86%). In four other studies, overall response rates were 82-89%. In addition to the cumulative BED or equivalent dose in 2 Gy fractions (EQD2), the interval between both radiotherapy courses <6 months and a BED per course ≥102 Gy2 (corresponding to an EQD2 ≥51 Gy2) were identified as risk factors for radiation myelopathy. Without these risk factors, a BED >120 Gy2 may be possible. Scoring tools have been developed that can assist physicians in estimating the risk of radiation myelopathy and selecting the appropriate dose-fractionation regimen of re-treatment. Reirradiation of MESCC may also be performed with highly-conformal radiotherapy. With IMRT or VMAT, rates of pain relief and improvement of neurologic symptoms of 60-93.5% and 42-73%, respectively, were achieved. One-year local control rates ranged between 55% and 88%. Rates of myelopathy or radiculopathy and vertebral compression fractures were 0% and 0-9.3%, respectively. With SBRT, rates of pain relief were 65-86%. Two studies reported improvements in neurologic symptoms of 0% and 82%, respectively. One-year local control rates were 74-83%. Rates of myelopathy or radiculopathy and vertebral compression fractures were 0-4.5% and 4.5-13.8%, respectively. For SBRT, a cumulative maximum EQD2 to thecal sac ≤70 Gy2, a maximum EQD2 of SBRT ≤25 Gy2, a ratio ≤0.5 of thecal sac maximum EQD2 of SBRT to maximum cumulative EQD2, and an interval between both courses ≥5 months were associated with a lower risk of myelopathy. Additional prospective trials are required to better define the options of reirradiation of MESCC.

Comparison of Mammographic Findings after Conventional Radiotherapy and forward Intensity-Modulated Radiation Therapy in Breast Conservative Therapy.

OBJECTIVE: This study aimed to determine and compare mammographic findings after conventional radiotherapy and forward intensity-modulated radiation therapy for breast conservation. METHODS: Eighty-six patients with BCT (373 mammograms) were included between 2010-2015 and had post-treatment mammograms available for review. All mammograms were taken with an 18 × 24 cm detector and 0.070 mm pixel size (Selenia Dimensions, Hologic, Marlborough, Massachusetts, US). We documented the radiation technique, dose, and mammographic findings (e.g., edema, thickening, scarring, and calcification). We tracked the stability duration for each patient and grouped mammographic findings into 1-, 2, and 3 years post-treatment. SPSS version 26 and Stata version 18 were used for analysis. RESULTS: The FIMRT group received a lower total radiation dose (p=0.030), a higher dose per fraction (p=0.030), and a lower maximum skin dose (p<0.001). The time to stable was shorter in the FIMRT group (975 days for CRT vs. 478 days for FIMRT; p=0.001). Among the 86 patients, the FIMRT group showed less breast parenchymal edema and noticeable scarring at 1, 2, and 3 years post-treatment than the CRT group, although the difference was not statistically significant. CONCLUSION: In the FIMRT group, post-BCT mammographic findings, including breast parenchymal edema and marked scar appearance, were fewer than those in the CRT group, and the duration to stable was significantly reduced.

Remineralization of lytic spinal metastases after radiation therapy - A retrospective cohort study comparing conventional external beam radiation therapy with stereotactic ablative body radiation.

Introduction: Osteolytic spinal metastases (SM) have a higher risk of fracture. In this study we aim to confirm the remineralization of lytic SM after radiation therapy. Secondary the influence of SBRT compared to cEBRT and tumor type will be analyzed. Methods: A retrospective cohort study was performed. Results: 87 patients, 100 SM were included. 29 received SBRT, 71 cEBRT. Most common primary tumors were breast (35 %), lung (26 %) and renal (11 %). Both cEBRT and SBRT resulted in a significant increase of bone mineral density (BMD) (83.76 HU ± 5.72 â†’ 241.41 HU ± 22.58 (p < 0.001) and 82.45 ± 9.13 â†’ 179.38 ± 47.83p = 0.026). There was a significant increase in absolute difference of BMD between the SM and reference vertebrae (p < 0.001). There was no significant difference between SBRT and cEBRT. There was no increase of BMD in renal lytic SM after radiation therapy (pre-treatment: 85.96 HU ± 19.07; 3 m 92.00 HU ± 21.86 (p = 0.882); 6 m 92.06 HU ± 23.94 (p = 0.902); 9 m 70.44 HU ± 7.45 (p = 0.213); 12 m 98.08 HU ± 11.24 (p = 0.740)). In all other primary tumors, a significant increase of BMD after radiation therapy was demonstrated (p < 0,05). Conclusion: We conclude that the BMD of lytic SM increases significantly after radiation therapy. Lytic SM of primary renal tumors are the exception; there is no significant remineralization of renal lytic SM after radiation therapy. There is no benefit of SBRT over cEBRT in this remineralization. These findings should be taken into account when deciding on surgery in the potentially unstable group defined by the spinal instability neoplastic score.

Hypofractionated versus conventional fractionation external beam radiotherapy in intermediate and high risk localized prostate cancer.

BACKGROUND: Prostate cancer is the second most common malignancy in men, and its incidence is increasing which is attributed to increased screening programs. The treatment options of intermediate and high risk prostate cancer include radical prostatectomy, radiotherapy and androgen deprivation therapy. Hypofractionated radiotherapy is becoming more popular lately due to better understanding of the radiobiology of prostate cancer and favorable logistics. OBJECTIVE: To compare the toxicity and efficacy of hypofractionated versus conventional fractionation external beam radiotherapy in patients with intermediate and high risk localized prostate cancer treated in Shaukat Khanum Memorial Hospital and Research Center, Lahore (SKMCH & RC). METHODOLOGY: We retrospectively conducted this study on histopathologically confirmed 114 patients with prostate adenocarcinoma who underwent treatment from January 2013 till December 2018. These patients were treated with radical radiotherapy along with hormonal therapy as per indication. Data was collected from electronic hospital system and analyzed by SPSS version 23. RESULTS: 114 patients were selected according to the inclusion criteria. Mean age was 68 years (61-75). 88% of patients had stage III-IVA disease at the time of diagnosis. Mean PSA and GS was 33 ± 39 SD and 7 ± 0.9 SD respectively. 89% (n = 102) received radiotherapy with 69% of patients receiving dose of 60 Gy in 20 fractions. Among patients who received hypofractionated dose, 86% (n = 61) of them were categorized as high risk and 14% (n = 10) were intermediate risk, whereas among conventional group 90% (n = 28) were high risk patients and 10% (n = 3) were of intermediate risk. In hypofractionated dose group, 14% (n = 10) developed grade 2 proctitis and 8% (n = 6) developed grade 2 cystitis, in contrast to conventional dose group in which only 3 patients (5%) developed grade 2 GI toxicity and 2 patients (2.9%) had grade 2 GU toxicity. However, these toxicities and their grade were clinically insignificant when compared with the dose groups (p = 0.11). 5 year overall survival for hypofractionated radiotherapy versus conventional dose was 100% and 90% respectively with 95% Cl and p value of 0.3 (clinically insignificant), whereas 5 year disease free survival was 100% and 75% for hypofractionation versus conventional EBRT respectively with 95% CI and p value of 0.04 (clinically significant). CONCLUSION: Hypofractionated radiotherapy in patients with intermediate and high risk localized prostate cancer has better disease free survival at the expense of higher risk for proctitis and cystitis but no difference in overall survival as compared to conventional dose of radiation.

Comparative study of concurrent conventional chemoradiotherapy versus hypofractionated chemoradiotherapy in newly diagnosed glioblastoma multiforme postoperative patients.

Purpose: To assess the treatment response and toxicity profile among two groups of newly diagnosed glioblastoma multiforme (GBM) postoperative patients receiving conventional radiotherapy (RT) versus hypofractionated RT with concurrent temozolomide (TMZ) in both. Materials and Methods: A total of 50 patients randomly allotted into two arms (25 in each). Dose received 60 Gy (2 Gy/#) in conventional fractionation RT versus 50 Gy (2.5 Gy/#) in hypofractionated RT with concurrent TMZ 75 mg/m2 orally daily in both arms, respectively. Follow-up was done at 1, 3, 6, and 12 months after completion of treatment to evaluate toxicities, treatment response, and progression-free survival (PFS). Results: All patients were well tolerated with treatment; no major adverse effects were monitored in two arms. There was no statistical significant difference in treatment response, which was found 64% versus 60% in arm A and arm B, respectively, at 3 months of follow-up (P = 0.768). Toxicity profiles were also noted similar in both arms. The 6-month PFS was 84% and 80% in arm A and arm B, respectively (P = 0.71) and 12-month PFS was 60% and 52% in arm A and arm B, respectively (P = 0.69). Conclusion: Among the patients followed, this study showed that hypofractionated RT regimen was not inferior to conventional RT regimen.

Radiotherapy Combination: Insight from Tumor Immune Microenvironment (TIME).

The view of Radiotherapy (RT) as a simple inducer of DNA damage resulting in tumor cell death has dramatically changed in recent years, and it is now widely accepted that RT can trigger an immune response which provides a sound basis for combining RT with immunotherapy. Given that, radiation can be delivered with different regimens, its effect on immune responses and Tumor Immune Microenvironment (TIME) may vary with dose and fractionation schedule. This fractional dose dependency may need to be more considered because of recent developments in RT delivery techniques making it possible to deliver precisely higher dosages per fraction (hypofractionation) while reducing exposure to normal tissues. Although combining radiotherapy with immunotherapy could be a promising strategy for synergistic enhancement of treatment efficacy, the selection of the best-matched combination of immunotherapy with each radiotherapy scheme remains to be addressed. Thus, for designing better therapeutic combinations, it is necessary to understand the immunological effects of RT. Here, we review the impact of conventional and different hypofractionation radiation schedules on the TIME. Subsequently, we highlight how knowing about these interactions may have implications for choosing a rational combination with targeted therapies.

Spectrum of Imaging Patterns of Lung Cancer following Radiation Therapy.

Radiation therapy using conventional or newer high-precision dose techniques, including three-dimensional conformal radiotherapy, intensity-modulated radiation therapy, stereotactic body radiation therapy, four-dimensional conformational radiotherapy, and proton therapy, is an important component of treating patients with lung cancer. Knowledge of the radiation technique used and the expected temporal evolution of radiation-induced lung injury, as well as patient-specific parameters such as previous radiotherapy, concurrent chemoradiotherapy, or immunotherapy, is important in image interpretation. This review discusses factors that affect the development and severity of radiation-induced lung injury and its radiological manifestations, as well as the differences between conventional and high-precision dose radiotherapy techniques.

Comparative Study of Hypo-Fractionated Radiotherapy Versus Conventional Radiotherapy in Breast Cancer.

BACKGROUND: Breast cancer is the most commonly diagnosed cancer causing death among females worldwide. Radiotherapy after lumpectomy/mastectomy in breast cancer cases is a successful treatment modality taking five weeks to complete. The aim of the present study is to compare the effectiveness of hypo-fractionated radiotherapy in breast cancer patients with conventional radiotherapy with respect to outcome and toxicity. METHODS: Sixty patients were randomly divided equally into a conventional group, Group A (dose: 50 Gy in 25 fractions), and a hypo-fractionated short-course radiotherapy group, Group B (dose: 40 Gy in 16 fractions). After thorough clinical and laboratory examination of all patients, the disease status was assessed prior to radiotherapy and three and six months after completion of radiotherapy. The cardiopulmonary function was assessed using echocardiography and pulmonary function tests prior to the procedure. The assessment of the development of toxicity (dysphagia, skin, lung, and lymphedema) was done during every clinical visit. RESULTS: The mean age of patients was 53.28 ± 9.73 years in Group A, and 55.67 ± 10.41 years in Group B (p=0.82). The right breast was involved in 13 (43.4%) patients in Group A and 14 (46.6%) in Group B, and the left breast was involved n 17 (56.6%) patients in Group A and 16 (53.4%) in Group B (p=0.81). Most of the patients were post-menopausal; 24 (80%) in Group A and 25 (83.4%) in Group B (p=0.91). Eleven (36.6%) patients were of stage T2N1M0 in both groups. However, no statistical difference was observed between the groups in the TNM (tumor, node, and metastasis) staging using the AJCC (American Joint Committee on Cancer) criteria (p=0.26). On comparing the responses in Group A and Group B, no significant difference was observed in either of the groups from immediate post-treatment to the 12-month follow-up period (p=0.53 and p=0.64, respectively). CONCLUSION: Hypo-fractionated radiotherapy is as effective as conventional radiotherapy and can be used as an alternative method for treatment following breast cancer surgery.

Radiation dose and schedule influence the abscopal effect in a bilateral murine CT26 tumor model.

Radiotherapy (RT) can induce immune-mediated responses in local irradiated tumors, and non-irradiated distant metastasis is termed the abscopal effect. Here, we aimed to evaluate the impact of different RT doses and fractions on anti-tumor responses within local irradiated and distance non-irradiated tumor microenvironments. In mice bearing CT26 tumors, the primary tumor was irradiated with three different RT doses (16 Gy × 1F, 10 Gy × 2F, and 3 Gy × 10F) with the same biologically effective dose. Tumor volumes and immune cells changes were assessed in irradiated and non-irradiated tumors. Survival times were evaluated over 90 days. Only 16 Gy × 1F radiation increased CD8 + T cells number in the irradiated (p = 0.043) and non-irradiated (p = 0.047) tumors compared to the untreated group. A high frequency of tumor-associated macrophages-1 (TAM-1) and low TAM-2 was found in 16 Gy × 1F irradiated mice. Moreover, 16 Gy × 1F significantly induced interferon gamma (IFNγ)-producing CD8 + cells in the spleen compared to controls (p = 0.021). Hypofraction regimens (16 Gy × 1F, 10 Gy × 2F) caused a reduction in myeloid-derived suppressor cells in the irradiated tumors. We detected A modest growth delay in both flank tumors and long-term survival after hypofraction treatments (16 Gy × 1F, 10 Gy × 2F). A single high RT dose increased CD8 + cells number in irradiated (p = 0.000) and non-irradiated (p = 0.002) tumors approximal up to 2 points along with significant induction of IFN-γ production by CD8 + cells in the spleen when combined with anti- programmed death ligand-1 (PDL-1) (p = 0.000). Combination therapy was also associated with bilateral tumor growth control and increased life span in mice. Hypofractionated RT schedules, especially single high dose, seem the most effective regimen for inducing an abscopal effect. Immune checkpoint inhibitors could promote RT-induced systemic effects.

Radiotherapeutic Outcomes for Localized Primary Rectal Mucosa-Associated Lymphoid Tissue Lymphoma: A Consecutive Case Series of Three Patients.

Gastrointestinal malignant lymphoma is uncommon and accounts for a small proportion of all gastrointestinal neoplasms. Primary rectal extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALToma) is a rare type of intestinal lymphoma. Here, we report about three patients (two females, one male) with localized rectal MALToma who were treated with external beam radiation therapy (EBRT). The median age of the patients was 59 years (range: 50-67 years). Chemotherapy or eradication therapy was not performed before EBRT. All patients received a radiation dose of 30 Gy in 15 fractions using X-ray photon beams. Pathological examination confirmed complete remission of rectal MALToma after EBRT in all patients. At approximately five years after EBRT, none of the patients showed any evidence of recurrence of rectal MALToma. The use of EBRT resulted in excellent disease control, and no severe radiation-induced toxicity was observed. These results suggest that EBRT is a useful treatment modality for primary rectal MALToma.

Clinical outcome of intensity-modulated radiotherapy versus two-dimensional conventional radiotherapy in locally advanced nasopharyngeal carcinoma: Comparative study at SKIMS Tertiary Care Institute.

Background: The management of nasopharyngeal cancer (NPC) at present is based primarily on radiotherapy, but the technique by which radiation therapy is delivered is different such as intensity-modulated radiotherapy (IMRT) and two-dimensional conventional radiotherapy (2D-CRT). Materials and Methods: In our study, IMRT and 2D-CRT were compared for their treatment outcome in locally advanced nasopharyngeal carcinoma (NPC) patients. Patients with Stage II to IVA nasopharyngeal cancer (NPC) as per the American Joint Committee on Cancer 7th and 8th edition 2017 treated with IMRT (n = 30) and 2D-CRT (n = 30) between October 2016 and October 2020 were retrospectively analyzed. We matched our patients by using the propensity-score matching method. OS was the primary endpoint of our study. The secondary endpoints were local relapse-free survival (LRFS), regional relapse-free survival (RRFS), disease-free survival (DFS), progression-free survival (PFS), and distant metastasis-free survival (DMFS). Acute and late radiation toxicities between IMRT and 2D-CRT were also compared. Results: In the propensity-matched cohort of 60 patients, 30 patients received 2D-CRT and 30 patients received IMRT. Compared with the treatment of 2D-CRT, the IMRT group is associated with a better 3-year OS (70% vs. 85% P = 0.045), LRFS (78% vs. 96% P = 0.047), RRFS (78% vs. 95% P = 0.015), DFS (80% vs. 95% P = 0.034), and PFS (84% vs. 90% P = 0.024), while as DMFS (85% vs. 85% P = 0.147) were comparable in both the groups. IMRT was also associated with a lower incidence of late toxicities such as xerostomia and trismus. Conclusion: Our study demonstrates that IMRT yields better long-term overall survival and local control including LRFS, RRFS, DFS, and PFS. In addition, late toxicities induced by irradiation in nasopharyngeal carcinoma (NPC) are lower with IMRT. IMRT may be an effective treatment in nasopharyngeal cancer (NPC) as compared to 2D-CRT, but further studies are needed to establish the association.

Predictive Factors Increasing the Risk of Radiation Toxicity in Patients with Early Breast Cancer.

OBJECTIVES: Radiation induces adverse events on healthy tissues which may be augmented by certain factors. This study aimed to assess patients; tumor and treatment-related factors which increase the risk of radiation-induced toxicity in breast cancer patients. METHODS: This prospective study included postmenopausal early breast cancer patients treated at the clinical oncology department, Assiut University, Egypt between January 2015 and December 2018. Patients treated with mastectomy followed by conventional radiotherapy (25x 2 Gy) and either concurrent or sequential letrozole. Acute and late radiation toxicity was scored according to EORTC/RTOG and risk factors were analyzed. RESULTS: A total of 75 patients were included in the study. After a median follow-up of 24 months, 12 patients had > grade 2 acute dermatitis, 5 patients had > grade 2 cardiac toxicity and 3 patients had > grade 2 lung toxicity. Multivariate analysis revealed that trastuzumab use was associated with a decrease risk of acute dermatitis (p= 0.01) but boost irradiation was significantly associated with increased risk of acute dermatitis (p= 0.01). Late toxicity > grade 2 was observed in 6 patients, 14 patients, and 2 patients for skin, heart, and lung respectively. CONCLUSION: The use of boost irradiation was associated with increased risk of acute dermatitis, in the contrary; the use of trastuzumab seemed to be protective as observed in this study.