Short-course Radiotherapy Research Articles

Postoperative complications in relation to overall treatment time in patients with rectal cancer receiving neoadjuvant radiotherapy.

The optimal timing of surgery for rectal cancer after radiotherapy (RT) is disputed. The Stockholm III trial concluded that it was oncologically safe to delay surgery for 4-8 weeks after short-course RT (SRT), with fewer postoperative complications compared with SRT with surgery within a week. Other studies have indicated that an even shorter interval between RT and surgery (0-3 days) might be beneficial. The aim of this study was to identify the optimal interval to surgery after RT. Patients were analysed as treated, in terms of overall treatment time (OTT), the interval from the start of RT until the day of surgery. Patients receiving SRT (5 × 5 Gy) were categorized according to OTT: 7 days (group A), 8-13 days (group B), 5-7 weeks (group C) and 8-13 weeks (group D). Patients receiving long-course RT (25 × 2 Gy) were grouped into those with an OTT of 9-11 weeks (group E) or 12-14 weeks (group F). Outcomes assessed were postoperative complications and early mortality. A total of 810 patients were analysed (group A, 100; group B, 247; group C, 192; group D, 160; group E, 52; group F, 59). Baseline patient characteristics were similar. There were significantly more overall complications in group B than in groups C and D. Adjusted odds ratios, with B as the reference group, were: 0·72 (95 per cent c.i. 0·40 to 1·32; P = 0·289), 0·50 (0·30 to 0·84; P = 0·009) and 0·39 (0·23 to 0·65; P < 0·001) for groups A, C and D respectively. Early mortality was similar in all groups. There were no significant differences between long-course RT groups. These results suggest that surgery should optimally be delayed for 4-12 weeks (OTT 5-13 weeks) after SRT.

The Financial Impact of Fractionation Scheme and Treatment Planning Method for Rectal Cancer in the United States

BackgroundPreoperative long-course chemoradiotherapy (CRT) and short-course radiotherapy (SCR) for locally advanced rectal cancer (LARC) were found to have equivalent outcomes in 3 randomized trials. SCR has not been widely adopted in the United States (US). Three-dimensional (3D) treatment planning is standard, whereas intensity-modulated radiotherapy (IMRT) is controversial. In this study, we assessed the economic impact of fractionation scheme and planning method for payers in the US. Materials and MethodsWe performed a population-based analysis of the total cost of radiotherapy for LARC in the US annually. The national annual target population was calculated using the Surveillance, Epidemiology, and End Results database. Radiotherapy costs were based on billing codes and 2018 pricing by Medicare's Hospital Outpatient Prospective Payment System. ResultsWe estimate that 12,945 patients with LARC are treated with radiotherapy annually in the US. The cost of CRT with 3D or IMRT is US $15,882 and $23,745 per patient, respectively. With SCR, the cost with 3D or IMRT is $5,458 and $7,323 per patient, respectively. The use of SCR would lead to 53% to 77% annual savings of $106,168,871 to $232,105,727 compared with CRT. IMRT increases the total cost of treatment by 34% to 50%, and if adopted widely, would lead to an excess cost of $24,152,134 and $101,784,723 annually with SCR and CRT, respectively. ConclusionsSCR may have the potential to save approximately US $106 to t232 million annually in the US, likely without impacting outcomes. Lack of evidence showing benefit with costly IMRT should limit its use to clinical trials. It would be reasonable for public and private payers to consider which type of radiation is most suited to reimbursement.

Planned Short-Course Radiation (scRT) is Superior to Upfront Concurrent Chemoradiation (CCRT) in Treating Metastatic Rectal Cancer

Background or PurposeTo compare the cost-performance between planned short-course radiation and upfront concurrent chemoradiation on metastatic rectal cancer. MethodsA total of 75 patients with metastatic rectal cancer who underwent planned short-course radiation or upfront concurrent chemoradiation were enrolled. The Kaplan-Meier method was used to compute the survival rates. The χ2 test was used to compare baseline characteristics. The Cox proportional hazards model was applied to determine the prognostic influence of clinicopathological factors. ResultsThe planned short-course radiation is superior to upfront concurrent chemoradiation in overall survival for the patients with metastatic rectal cancer (34.8 vs. 20.2 months, P = 0.010). The planned short-course radiation was an independent prognostic factor (P = 0.009, HR (95% CI) = 0.319(0.135–0.752)). The efficacy of radiation on downstaging was similar between planned short-course radiation and upfront concurrent chemoradiation. The total cost of concurrent chemoradiation is 4.52-fold more expensive than that of short-course radiation (340,142 vs. 75,106 NT dollars, respectively). ConclusionsBased on the impressive cost-performance of planned short-course radiation compared with upfront concurrent chemoradiation (better OS, modest downstaging and lower cost), planned short-course radiation should be the preferred radiation approach for managing metastatic rectal cancer.

The financial impact of fractionation scheme and treatment planning method for rectal cancer in the United States.

6518 Background: Preoperative long-course chemoradiotherapy (CRT) and short-course radiotherapy (SCR) for locally advanced rectal cancer (LARC) were found to have equivalent outcomes in three randomized trials. SCR may have lower acute toxicity and the down-staging following CRT is more well-established. At present, SCR is frequently used in Europe but has not been widely adopted in the United States (US). It is standard to deliver radiotherapy by 3D planning, while the use of Intensity-modulated radiotherapy (IMRT) is controversial. In recent years there has been an increasing focus on understanding the cost and value of cancer care. In this study we aimed to assess the economic impact of fractionation scheme and treatment planning method for payers in the US. Methods: We performed a population-based analysis of the total cost of radiotherapy for LARC in the US annually. The national annual target population of patients was calculated using the Surveillance, Epidemiology, and End Results (SEER) database. Treatment costs for various fractionation schemes were based on billing codes and 2018 pricing by Medicare's Hospital Outpatient Prospective Payment System (OPPS). The cost of chemotherapy was based on the Payment Allowance Limits for Medicare Part B Drugs by Centers for Medicare and Medicaid Services (CMS). Results: We estimate that 12,945 patients with LARC are treated with radiotherapy annually in the US. The cost of CRT with 3-D or IMRT is US$ 15,881.76 and US$ 23,744.82 per patient, respectively. With 3-D SCR the cost is US$ 5,457 per patient. The use of SCR would lead to 64-77% annual savings of US$ 125,701,387 - US$ 236,727,934 in the US compared with 3-D and IMRT based CRT, respectively. IMRT based planning increases the total cost of CRT by 49% and if adopted widely would lead to an excess cost of US$ 101,787,312 annually. Conclusions: SCR may have the potential to save in the region of US$ 0.12-0.23 billion annually in the US, likely without impacting outcomes. Lack of evidence showing benefit with costly IMRT should limit its use to clinical trials. SCR may also lead to lower personal financial toxicity. It would be reasonable for public and private payers to consider which type of radiation is most suited to reimbursement.

Safety and Efficacy of Pre-Operative, Short Course Radiation Therapy for Prostate Cancer: Results From a Phase I Trial

Up to 60% of patients (pts) with prostate cancer that extends beyond the prostatic capsule will have positive resection margins following radical prostatectomy. Post-operative radiation therapy (PostOp) is routinely offered to those pts. Although this improves local control and overall survival, it results in significantly more late toxicity than surgery alone. Pre-operative radiation therapy (PreOp) has become the standard for soft tissue sarcoma and rectal cancer, improving local control and reducing toxicity compared to PostOp. We report the results of a Phase I trial, investigating the use of PreOp for prostate pts at high risk of extra-capsular extension. Following REB approval, prostate cancer pts at high risk of extra-capsular extension were prospectively identified for inclusion based on T-stage, N-stage, PSA and Gleason score. Since this was a Phase I study of safety and efficacy for a novel treatment regimen, a small sample size was used (15 pts). Patients received 25 Gy in 5 daily fractions to the prostate-only, followed by a radical prostatectomy 1-2 weeks after RT completion. Study endpoints were descriptive in nature due to the small sample size, and included intra-operative morbidity, early, late and ultra-late urinary (U) and gastrointestinal (GI) toxicity (using RTOG and CTCAE grading (G) systems). Between 2001 and 2004, 15 pts enrolled in the trial and all received 25 Gy over 5 consecutive fractions. Fourteen pts were irradiated with a 6-field conformal plan, and one with IMRT. Planning constraints were used to limit the dose to the femoral heads, bladder and rectal walls. Patients were treated with a full bladder / empty rectum protocol, employing daily portal image guidance based on intra-prostatic markers. G2 diarrhea (1 pt) and G2 cystitis (1 pt) were reported during RT. Fourteen pts went on to receive a non-nerve sparing radical retropubic prostatectomy, which included bilateral lymph node dissection for 13 pts. Four pts required a blood transfusion, and 3 pts had adhesions surrounding the prostate. Surgical margins were positive in 7 pts, PSA was detectable immediately after surgery in 5 pts. By 45 months, one patient had reported one episode of rectal bleeding that resolved with corticosteroids. Eleven pts reported urinary incontinence (73%), 3 had a urethral stricture (20%), and 1 reported G2 intermittent haematuria. To date, the median follow-up is 147 months. Two pts (14%) report G2 U toxicity, and 6 pts (43%) G3 U toxicity. One patient experienced transient G2 proctitis. At last follow-up, 8 (57%) and 6 (43%) pts have biochemical and metastatic progression, respectively. There were two prostate cancer related deaths. Delivery of short-course radiation therapy followed by an immediate prostatectomy is feasible. However, the incidence of late U toxicity is approximately 3-fold higher in this study than in Phase III trials of PostOp, with no appreciable benefit in biochemical or metastases free survival compared to those PostOp studies. Future studies of this regimen must be cautiously considered, and should include radiotherapy and surgical advances that might reduce toxicity, and multiparametric and/or molecular imaging to more precisely identify pts who may benefit from such an approach. This study emphasizes the need for long term follow-up data to fully appreciate the toxicity of such novel approaches.

Surgical complications after different therapeutic approaches for locally advanced rectal cancer.

BACKGROUNDPreoperative radiochemotherapy is widely used in locally advanced rectal cancer. It can improve local control of rectal cancer. However, some researchers believe it increases the incidence of surgical complications. They doubt its safety. Patients with locally advanced rectal cancer receive three different treatments in our hospital, including long-course radiochemotherapy, short-course radiotherapy, and surgery directly. We can compare their differences in postoperative complications.AIMTo investigate surgical complications caused by different preoperative radiotherapy regimens.METHODSWe retrospectively analyzed 1197 patients admitted between 2008 and 2010 with locally advanced rectal cancer. Three hundred and forty-six patients were treated with preoperative long-course radiochemotherapy (25 × 2 Gy) followed by total mesorectal excision (TME) 6–8 wk later, and 259 patients received short-course radiotherapy (10 × 3 Gy) and subsequently TME 7–10 d later. The remaining 592 patients underwent TME alone without neoadjuvant therapy. According to Clavien–Dindo classification, surgical complications were evaluated for up to 30 d after discharge from hospital.RESULTSThere were no deaths in 30 d in all groups after treatment. The major complications were anastomotic leakage and perineal wound complications. The results suggested that both long-course [odds ratio (OR) = 3.624, 95% confidence interval (CI): 1.689–7.775, P = 0.001] and short-course (OR = 5.150, 95%CI: 1.828–14.515, P = 0.002) radiotherapy were associated with anastomotic leakage. Temporary ileostomy was a protective factor for anastomotic leakage (OR = 6.211, 95%CI: 2.525–15.385, P < 0.001). The severity of anastomotic leakage did not increase in patients following preoperative radiotherapy (P = 0.411). Compared with TME alone, short-course radiotherapy was associated with an increase in perineal wound complications (OR = 5.565, 95%CI: 2.203–14.057, P < 0.001), but long-course radiotherapy seemed safe regarding this complication (OR = 1.692, 95%CI: 0.651–4.394, P = 0.280). Although the severity of perineal wound complications increased in patients following short-course radiotherapy (P < 0.001), additional intervention was not necessary.CONCLUSIONRadiotherapy increased the incidence but not severity of anastomotic leakage. Short-course radiotherapy was also accompanied with perineal wound complications, but intervention appeared unnecessary to ameliorate the complications.

The treatment of rectal cancer with synchronous liver metastases: A matter of strategy.

Around one fifth of patients with rectal cancer (RC) have synchronous metastatic disease at the diagnosis. The optimal treatment sequence for patients with RC and synchronous liver metastases (LM) is complex and unclear, missing strong, evidence-based recommendations. From a clinical point of view, this situation is highly heterogeneous and the treatment strategy is generally determined by a number of factors, such as the potential resectability of primary tumor and LM, patients' characteristics, the presence of primary tumor-related symptoms and the response to therapies. Treatment options for these patients include systemic therapy, short-course radiotherapy (SC-RT), long-course chemoradiotherapy (LC-CRT) and surgery of the primary tumor and LM. The principal goal is to render the patients eligible to radical surgery, thus offering a chance of cure at least for some of them. This review summarizes the most appropriate treatment strategies which should be recommended in the different clinical scenarios of this heterogeneous condition.

Phase 1 Study of Neoadjuvant Short-Course Radiation Therapy Concurrent With Infusional 5-Fluorouracil for the Treatment of Locally Advanced Rectal Cancer

PurposeTo assess the safety and feasibility of neoadjuvant short-course radiation therapy (RT) concurrent with continuous infusion 5-fluorouracil (5-FU) for the treatment of locally advanced rectal cancer. Methods and MaterialsPatients with cT3-4 or N + rectal adenocarcinoma based on ultrasound or magnetic resonance imaging were prospectively enrolled in this study. Study treatment consisted of continuous infusion 5-FU combined with short-course RT (5 Gy x 5 fractions) followed by 4 cycles of mFOLFOX, total mesorectal excision (TME), and 6 cycles of adjuvant mFOLFOX. To mitigate the potential added toxicity from concurrent 5-FU, intensity modulated RT was used. Using the continual reassessment method, the dose of 5-FU was escalated from 100 to a maximum-tolerated dose of 200 mg/m2/d. ResultsFourteen patients were accrued. All patients completed continuous infusion 5-FU and short-course RT and the 5-FU dose was safely escalated to 200 mg/m2/d with no dose-limiting toxicity. Thirteen patients received the neoadjuvant mFOLFOX, and only 1 patient went straight to surgery after chemoradiation. Clinical response was 21% complete, 63% partial, 14% stable disease, and no patients had progression. Three patients with cCR had negative biopsies and did not have TME. Pathologic response was 64% partial response and 14% stable disease. No patients had pathologic progression. The most common grade 3 and 4 toxicities were cytopenias. The most common grade 1 and 2 toxicities were cytopenia, fatigue, diarrhea, and nausea. ConclusionsOur findings suggest that concurrent chemotherapy with neoadjuvant short-course RT is feasible and can be safely given with concurrent continuous infusion 5-FU. This works adds to the growing evidence that short-course RT is not only equivalent to long-course RT, but also may provide additional benefits, such as allowing for a transition to full dose systemic therapy in the neoadjuvant setting, selective organ preservation in complete responders, and providing a more convenient and cost-effective way of delivering pelvic RT.

128P - Role of short-course radiotherapy in post-operative carcinoma of the breast

128P - Role of short-course radiotherapy in post-operative carcinoma of the breast

Determining the use of preoperative (chemo)radiotherapy in primary rectal cancer according to national and international guidelines

BackgroundPre-operative radiotherapy (RT) or chemoradiotherapy (CRT) is frequently used prior to rectal cancer surgery to improve local control and survival. The treatment is administered according to guidelines, but these recommendations vary significantly between countries. Based on the stage distribution and risk factors of rectal cancers as determined by magnetic resonance imaging (MRI) in an unselected Swedish population, the use of RT/CRT according to 15 selected guidelines is described. Materials and methodsSelected guidelines from different countries and regions were applied to a well-characterized unselected population-based material of 686 primary non-metastatic rectal cancers staged by MRI. The fraction of patients assigned to surgery alone or surgery following pre-treatment with (C)RT was determined according to the respective guideline. RT/CRT administered to rectal cancer patients for other reasons, for example, for organ preservation or palliation, was not considered. ResultsThe fraction of patients with a clear recommendation for pre-treatment with (C)RT varied between 38% and 77% according to the different guidelines. In most guidelines, CRT was recommended to all patients who were not operated directly, and, in others, short-course RT was also recommended to patients with intermediate risk tumours. If only non-resectable or difficult to resect tumours were recommended pre-treatment, as stated in many Japanese publications, 9% would receive CRT followed by a delay to surgery. ConclusionsAccording to most guidelines, well over 50% of primary non-metastatic rectal cancer patients from a general population, in which screening for colorectal cancer is not practised, are recommended treatment with pre-operative/neo-adjuvant therapy.

Do Acellular Mucin Pools in Resection Margins for Rectal Cancer Influence Outcomes?

Positive resection margins predict poor prognosis in rectal cancer (RC). Literature on the impact of acellular mucin (ACM) in circumferential resection margin (CRM) or distal resection margin (DRM) of proctectomy specimens on RC recurrence and outcomes is lacking. The retrospective study was conducted to determine the oncological outcomes of the RC patients with ACM in or within 1mm of margins of the rectal resection specimens. Histopathology reports of RC resection specimens dated from June 2013 till May 2016 were reviewed to identify cases with ACM in CRM (n = 10) and DRM (n = 2). Relevant details of these patients were gathered from the electronic medical record. Pattern of recurrence was studied. In cases with only ACM in CRM (n = 10), disease (primary tumor or nodes) was radiologically reaching the mesorectal fascia except two, who had extra mesorectal nodes. Median distance of tumor from anal verge was 2cm. All patient received neoadjuvant therapy: four patients received chemoradiotherapy (NACTRT), one received short-course radiotherapy, and five received NACTRT followed by neoadjuvant chemotherapy. Abdominoperineal resection, intersphincteric resection and total pelvic exenteration were done for six, three, and one patient, respectively. In two additional cases of anterior resection with ACM in DRM, one underwent upfront resection while the other received NACTRT. Over a mean follow-up period of 43months, four patients developed recurrences. Two of them had local recurrence and only one had isolated local recurrence. ACM in resection margins of RC resection specimens does not seem to increase likelihood of local recurrence.

Cost-effectiveness of Short-Course Radiation Therapy vs Long-Course Chemoradiation for Locally Advanced Rectal Cancer

Although both short-course radiotherapy and long-course chemoradiotherapy have been practiced in parallel for more than 15 years, no cost-effectiveness analysis comparing these 2 approaches in patients with locally advanced rectal cancer has been published. To analyze the cost-effectiveness of short-course radiotherapy vs long-course chemoradiotherapy for the treatment of patients with locally advanced rectal cancer. This economic evaluation used a cost-effectiveness model simulating 10-year outcomes for 1 million hypothetical patients aged 65 years with locally advanced rectal cancer treated with either short-course radiotherapy or long-course chemoradiotherapy, followed by surgery and chemotherapy. Utilities and probabilities from the literature and costs from the Healthcare Bluebook and Medicare fee schedules were used to determine incremental cost-effectiveness ratios. It was assumed that long-course chemoradiotherapy would result in higher rates of low anterior resection (LAR). To model preference-sensitive care, a 2-way sensitivity analysis was conducted in which the utilities of the no-evidence-of-disease (NED) states with LAR and abdominoperineal resection (APR) were simultaneously varied. The analysis was repeated for patients with distal rectal tumors. Analysis was conducted from January to October 2018. Short-course radiotherapy and long-course chemoradiotherapy. Incremental cost-effectiveness ratios. Short-course radiotherapy was the cost-effective strategy compared with long-course chemoradiotherapy (incremental cost-effectiveness ratio, $133 495 per quality-adjusted life-year). Two-way sensitivity analysis revealed that the cost-effective approach for a given patient depended on the utilities for the NED-LAR and NED-APR states. Assuming that a greater proportion of patients with locally advanced distal tumors undergoing long-course chemoradiotherapy (39%) would proceed to LAR compared with those treated with short-course radiotherapy (19%), long-course chemoradiotherapy was the cost-effective approach (incremental cost-effectiveness ratio, $61 123 per quality-adjusted life-year). Short-course radiotherapy was the cost-effective strategy compared with long-course chemoradiotherapy for patients with locally advanced rectal cancer. The cost-effectiveness of short-course radiotherapy vs long-course chemoradiotherapy was sensitive to the utilities of the NED-LAR and NED-APR health states, highlighting the importance of care that is sensitive to patient preference. Long-course chemoradiotherapy was the cost-effective approach for patients with distal tumors.

Preoperative Short-Course Radiation Therapy in Rectal Cancer

Preoperative Short-Course Radiation Therapy in Rectal Cancer

Short course radiation therapy for rectal cancer in the elderly: can radical surgery be avoided?

Rectal cancer in elderly patients can be difficult to manage. Short course radiation therapy (SCRT) has shown to be effective when given immediately prior to surgery. Here we report outcomes of elderly patients who underwent SCRT either alone or prior to resection. Between 2010 and 2015, elderly patients with rectal cancer and no distant metastatic disease were identified. Symptoms at diagnosis, therapies, toxicities, and pathologic and clinical response were recorded from patient charts. The SCRT prescription dose was 5 Gy ×5 to the rectal tumor and 4 Gy ×5 to the mesorectum, omitting the iliac nodes. Twenty patients were identified with median age of 85 years (range, 71-93 years). No patient received systemic therapy. Sixty percent of patients were cT3 at diagnosis. Half underwent resection post SCRT and half received SCRT as definitive therapy. The 1- and 2-year overall survival was 75% and 54%. Overall survival did not differ between patients treated with SCRT and surgery compared to SCRT alone (P=0.8). Of the 10 surgical patients, 3 had a complete pathologic response at time of resection and 3 patients died within 2 weeks due to perioperative complications. Of patients treated with SCRT alone, 8 were symptomatic at presentation and 5 had a clinician defined symptomatic response. No patient treated with SCRT monotherapy required additional palliative measures for outflow obstruction, but 2 progressed locally and died. SCRT is well tolerated, results in pathologic complete responses in a small percentage of patients, and achieves 63% symptom improvement rate as monotherapy. A high peri-operative complication rate was observed in this small series. In elderly patients, SCRT as initial treatment with a watch and wait approach for surgery is feasible and should be evaluated prospectively.

Systemic chemotherapy and short-course radiation in metastatic rectal cancers: A feasible paradigm in unresectable and potentially resectable cancers.

Background:The optimal use and sequencing of short-course radiotherapy (SCRT) in metastatic rectal cancers (mRCs) are not well established.Materials and Methods:We retrospectively reviewed the records of mRC patients receiving SCRT followed by palliative chemotherapy between January 1, 2013, and December 31, 2016, in Tata Memorial Hospital. Patients were classified as having “potentially resectable” disease (local and metastatic) or “unresectable” disease at baseline based on prespecified criteria.Results:A total of 105 consecutive patients were available for analysis. The median age of patients was 48 years (range: 16–62 years), and 57.1% were male patients. Signet ring histology was seen in 13.3% of patients. The most common site of metastases was liver limited (29.5%), nonloco-regional nodes (12.4%), and lung limited metastases (9.5%). Chemotherapeutic regimens administered were capecitabine-oxaliplatin (70.5%), modified 5 fluorouracil (5 FU)-leucovorin-irinotecan-oxaliplatin (10.5%), and modified 5 FU-leucovorin-irinotecan (8.6%). Targeted therapy accompanying chemotherapy was administered in 27.6% of patients. About 42.1% of patients with potentially resectable disease and 11.1% with the unresectable disease at baseline underwent curative-intent resection of the primary and address of metastatic sites. With a median follow-up 18.2 months, median overall survival (OS) was 15.7 months (95% confidence interval: 10.42–20.99). Patients classified as potentially resectable had a median OS of 32.62 months while patients initially classified as unresectable had a median OS of 13.04 months (P = 0.016). The presence of signet ring morphology predicted for inferior mOS (P = 0.021).Conclusions:SCRT followed by systemic therapy in mRC is a feasible, efficacious paradigm for maximizing palliation, and achieving objective responses. The classification of patients based on resectability was predictive of actual resection rates as well as outcomes. Signet ring mRC show inferior outcomes in this cohort of patients.

PO-0820 Effect of short-course radiotherapy on postoperative complications in locally advanced rectal cancer

PO-0820 Effect of short-course radiotherapy on postoperative complications in locally advanced rectal cancer

The role of radiotherapy in the management of non-melanoma skin cancer.

The global incidence of non-melanoma skin cancer continues to increase as the global population ages with the highest incidence in the world occurring in Australian and New Zealand patients. There are numerous treatment options available for non-melanoma skin cancer patients of which radiotherapy is an efficacious and versatile tissue preserving non-surgical (or medical) option. In patients where excision may not be an option (medically/technically inoperable) or considered less ideal (e.g. cosmetic outcome), radiotherapy offers an excellent option. Following surgery, adjuvant radiotherapy in patients with unfavourable pathology can decrease the risk of recurrence and associated morbidity. Elderly and co-morbid patients with poor performance status can benefit from short-course hypofractionated radiotherapy in the setting where surgery is not an option. As with any modality, radiotherapy has advantages and disadvantages and it is therefore important for clinicians to appreciate these. We aim to present an update for clinicians that manage patients with non-melanoma skin cancer on the role of radiotherapy.

Locally advanced rectal adenocarcinoma: Are preoperative short and long course radiotherapy truly equivalent?

In the neoadjuvant treatment of locally advanced rectal adenocarcinoma, long- and short-course radiotherapy are considered to be of equivalent efficacy based upon several randomized trials. The present study assessed the effect of radiotherapy dose on overall survival. Using the National Cancer Database (2006-2013) 458 individuals with clinical stage II/III rectal adenocarcinoma treated were identified, with either short- (25 Gy) or long- (45 or 50.4 Gy) course neoadjuvant radiotherapy followed by surgery, without neoadjuvant or adjuvant chemotherapy. Multivariate COX regression was employed to evaluate differences in overall survival according to radiotherapy regimen. An association with improved overall survival in individuals treated with long- compared with short-course radiotherapy was demonstrated (HR=0.50, 0.34-0.73). The 30- and 90-day post-surgery mortality rates were higher in the short-course group when compared with the long-course group (12.2 vs. 2.4%; and 18.5 vs. 5.4%, respectively). Following the exclusion of patients that succumbed within 90-days post-surgery, overall survival advantage in the long-course group compared with the short-course group was maintained [hazard ratio (HR)=0.62, 0.39-0.99], with a median overall survival of 25.3 months (IQR 16.9-41.6) for the short-course group compared with 43.5 months (IQR 25.6-67.9) for the long-course group. To the best of our knowledge, the present results suggest for the first time that long-course radiotherapy is associated with an improved overall survival compared with short-course radiotherapy in locally advanced rectal adenocarcinoma in the absence of chemotherapy usage. This possible advantage is clinically relevant mainly in patients who cannot tolerate systemic chemotherapy.

Glioblastoma in Elderly Patients: Current Management and Future Perspectives.

The incidence of glioblastoma (GBM) in the elderly population is slowly increasing in Western countries. Current management includes surgery, radiation therapy (RT) and chemotherapy; however, survival is significantly worse than that observed in younger patients and the optimal treatment in terms of efficacy and safety remains a matter of debate. Surgical resection is often employed as initial treatment for elderly patients with GBM, although the survival benefit is modest. Better survival has been reported in elderly patients treated with RT compared with those receiving supportive care alone, with similar survival outcome for patients undergoing standard RT (60 Gy over 6 weeks) and hypofractionated RT (25–40 Gy in 5–15 daily fractions). Temozolomide, an alkylating agent, may represent an effective and safe therapy in patients with promoter methylation of O6-methylguanine-DNA-methyltransferase (MGMT) gene which is predictor of responsiveness to alkylating agents. An abbreviated course of RT, 40 Gy in 15 daily fractions in combination with adjuvant and concomitant temozolomide has emerged as an effective treatment for patients aged 65 years old or over with GBM. Results of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG CE6) and European Organization for Research and Treatment of Cancer (EORTC 26062/22061) randomized study of short-course RT with or without concurrent and adjuvant temozolomide have demonstrated a significant improvement in progression-free survival and overall survival for patients receiving RT and temozolomide over RT alone, without impairing either quality of life or functional status. Although combined chemoradiation has become the recommended treatment in fit elderly patients with GBM, several questions remain unanswered, including the survival impact of chemoradiation in patients with impaired neurological status, advanced age (>75–80 years old), or for those with severe comorbidities. In addition, the efficacy and safety of alternative therapeutic approaches according to the methylation status of the O6-methylguanine-DNA methyl-transferase (MGMT) gene promoter need to be explored in future trials.

Dose escalation of preoperative short-course radiotherapy followed by neoadjuvant chemotherapy in locally advanced rectal cancer: protocol for an open-label, single-centre, phase I clinical trial

IntroductionPreoperative radiotherapy followed by total mesorectal excision with adjuvant chemotherapy has been recommended as the preferred treatment method for locally advanced rectal cancer (LARC). Similar rates of local control, survival...