Short-course Radiotherapy Research Articles

Short-Course Radiotherapy Based Total Neoadjuvant Therapy Combined with Toripalimab for Locally Advanced Rectal Cancer: Preliminary Findings from a Randomized, Prospective, Multicenter, Double-Arm, Phase II Trial (TORCH)

<h3>Purpose/Objective(s)</h3> For patients with locally advanced rectal cancer (LARC), the standard treatment is neoadjuvant chemoradiotherapy combined with curative surgery. Total neoadjuvant therapy (TNT) has been used to increase rates of complete response and organ preservation, and achieve early control of distant metastasis. Recently, hypofractionated radiotherapy shows better synergistic effects in combination with PD-1/PD-L1 antibodies than conventional fractionated radiotherapy. Thus, the combination of short-course radiotherapy (SCRT) based TNT and immunotherapy is likely to further improve both tumor response and prognosis for LARC patients. <h3>Materials/Methods</h3> TORCH is a randomized, prospective, multicenter, double-arm, phase II trial. 130 LARC (T3-4/N+M0, distance from anus ≤10cm) patients will be treated with TNT approach and assigned to the consolidation arm (A) and induction arm (B). Arm A will receive SCRT (25 Gy/5Fx), followed by 6 cycles of Toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Arm B will first receive 2 cycles of ToriCAPOX, then receive SCRT, followed by 4 cycles of ToriCAPOX. Both groups will receive curative surgery or W&W strategy. The primary endpoint is the rate of complete response (CR, pCR plus cCR). The secondary endpoints include the grade 3-4 acute adverse effects (AE) rate, 3-year DFS rate, 3-year OS rate, etc. The "pick the winner" method is used to investigate the better regimen. <h3>Results</h3> Up to February 20, 2022, 81 patients have been recruited in the trial. A total of 16 patients (all MSS; arm A: 7, arm B: 9) have completed all neoadjuvant therapy. Most of them showed high risk factors of recurrence, including lower location (≤5cm, 14/16), deeper primary lesion invasion (cT4/MRF+, 7/16) and more positive lymph nodes (cN2, 9/16). Finally, 5 patients (arm A: 1, arm B: 4) achieved cCR and decided to adopt W&W strategy. 11 patients received surgery (Dixon: 6, Miles: 5) and the pathological results showed 8 cases of pCR (arm A: 4, arm B: 4), one near-pCR (arm A) and two non-pCR (arm A: 1, arm B: 1). Thus, the CR rate was amazingly high (CR rate: 81.25%, 13/16; pCR rate: 72.73%, 8/11). Even 6 patients who were evaluated as ycT3/N+/MRF+/EMVI+ before surgery was still demonstrated to be pCR after strict pathological examination. The only grade 3 AE was thrombocytopenia (37.50%, 6/16). And no grade 4 AE was observed. <h3>Conclusion</h3> SCRT base TNT combined with Toripalimab have achieved surprisingly excellent CR rate and good tolerance in LARC patients (in our cohort), which has the potential to improve organ preservation rate. In the future, this ongoing trial will demonstrate this efficacy and compare the two arms by larger sample size.

Cost Minimization Analysis of Conventional vs. Short-Course Radiotherapy with Temozolomide for Non-Elderly Patients with Newly Diagnosed Glioblastoma

<h3>Purpose/Objective(s)</h3> Standard of care for adults aged 70 years or younger with an ECOG performance status of 0-2 and newly diagnosed glioblastoma is maximal safe resection followed by radiotherapy/RT (60 Gy in 30 fractions) with concurrent temozolomide/TMZ (75mg/m2) followed by 6-12 months of adjuvant TMZ (150-200 mg/m2). Recently a phase III non-inferiority trial compared conventional (60 Gy in 30 fractions) RT with TMZ versus short-course (60 Gy in 20 fractions) RT with TMZ and found that short-course RT with TMZ was non-inferior on two separate interim analyses conducted to date. <h3>Materials/Methods</h3> We performed a cost minimization analysis to determine the cost savings of short-course RT with TMZ versus conventional RT with TMZ for patients with newly diagnosed glioblastoma. All the resources necessary to deliver the two treatment regimens including the time and expertise of various health care professionals, supplies, infrastructure, and other means were identified by experienced clinicians at our institution. Shared costs between the two different treatment regimens were identified, as they cancel each other out, and were not included in our analysis. Costs were obtained from several sources including institutional databases, collective bargaining agreements, Minister of Health cost documents, and expert elicitation. All costs were analyzed in 2022 Canadian dollars (CAD). Any cost parameters used within the model that are older than the year 2021 were inflation adjusted using the Bank of Canada inflation adjustment calculator. <h3>Results</h3> The non-shared treatment costs of one patient treated using conventional RT with TMZ versus short-course RT with TMZ was $22 532.97 and $15 021.98 respectively. Short-course RT with TMZ therefore saves $7510.89 dollars per patient treated relative to conventional RT with TMZ. For every 60 patients treated with short-course RT with TMZ, the salary of one full time radiation oncology staff position equivalent in Alberta and 600 treatment slots are recovered <h3>Conclusion</h3> For patients with newly diagnosed glioblastoma, short-course RT with TMZ leads to cost savings compared to conventional RT with TMZ. Short-course RT with TMZ also reduces the number of treatment slots needed for these patients, which has potential for improved wait times and access to RT for other cancer patients.

Racial Disparities in Palliative Radiation for African American Men with Metastatic Prostate Cancer

<h3>Purpose/Objective(s)</h3> African American (AA) men with prostate cancer (PCa) are at higher risk of aggressive and metastatic disease when compared with non-Hispanic White (NHW) men. Palliative radiation offers effective pain alleviation from symptomatic lesions, though little is known about the patterns of palliative radiation usage for AA vs. NHW men. We evaluated whether receipt of palliative radiation differs between AA and NHW men and investigated whether AA men receive different palliative radiation treatment courses. <h3>Materials/Methods</h3> We identified men 65 and older, diagnosed with metastatic PCa from 2004-2013 within the Surveillance, Epidemiology, and End Results (SEER) – Medicare database. Palliative radiation usage, including number of fractions, courses, and use of intensity-modulated radiation therapy (IMRT), was delineated through Medicare reimbursement claims. Short-course was defined as ≤5 fractions. Multivariable logistic regression assessed the influence of AA race on receiving palliative radiation. AA men are often diagnosed at younger age than NHW men, so we included the interaction between age and AA race in another multivariable model. For patients who received palliative radiation, we used separate multivariable logistic regressions to evaluate the impact of AA race on receiving short-course radiation, >1 course of radiation, and IMRT. <h3>Results</h3> The cohort included 7,954 men (6,552 NHW and 1,402 AA). Median age was 77 with median follow-up of 32 months. Median age for AA men: 74; NHW men: 78. A total of 1,926 patients received palliative radiation (1,628 NHW and 298 AA). On multivariable analysis, AA men had 25% reduced odds of receiving palliative radiation (odds ratio (OR), 95% confidence interval (CI): 0.75, [0.65-0.87], <i>P</i><0.01). For each year above age 65, AA men had 2% reduced odds of receiving palliative radiation when compared to NHW men (OR, 95% CI: 0.98, [0.96-0.99], <i>P_interactio</i>_n: 0.04). For those undergoing palliative radiation, multivariable analysis revealed no significant difference between AA and NHW men for receiving >1 course, short-course vs long-course radiation, and IMRT. <h3>Conclusion</h3> In this large national cohort of Medicare patients, AA race was associated with reduced odds of receiving palliative radiation, a disparity most pronounced for older AA men. Our results suggest that the racial disparity in palliative radiation exists predominantly prior to initiation of therapy. AA men who received palliative radiation displayed similar fractionation, number of courses, and usage of IMRT when compared to NHW men. Increased counseling for AA men with metastatic PCa must be emphasized to ensure AA men have equal opportunity to the benefits of palliative radiation.

Dosimetric predictors of toxicity in a randomized study of short-course vs conventional radiotherapy for glioblastoma

PurposeThere is no consensus on appropriate organ at risk (OAR) constraints for short-course radiotherapy for patients with glioblastoma. Using dosimetry and prospectively-collected toxicity data from a trial of short-course radiotherapy for glioblastoma, this study aims to empirically examine the OAR constraints, with particular attention to left hippocampus dosimetry and impact on neuro-cognitive decline. Methods and MaterialsData was taken from a randomized control trial of 133 adults (age 18–70 years; ECOG performance score 0–2) with newly diagnosed glioblastoma treated with 60 Gy in 30 (conventional arm) versus 20 (short-course arm) fractions of adjuvant chemoradiotherapy (ClinicalTrials.gov Identifier: NCT02206230). The delivered plan’s dosimetry to the OARs was correlated to prospective-collected toxicity and Mini-Mental State Examination (MMSE) data. ResultsToxicity events were not significantly increased in the short-course arm versus the conventional arm. Across all OARs, delivered radiation doses within protocol-allowable maximum doses correlated with lack of grade ≥ 2 toxicities in both arms (p < 0.001), while patients with OAR doses at or above protocol limits correlated with increased grade ≥ 2 toxicities across all examined OARs in both arms (p-values 0.063–0.250). Mean left hippocampus dose was significantly associated with post-radiotherapy decline in MMSE scores (p = 0.005), while the right hippocampus mean dose did not reach statistical significance (p = 0.277). Compared to the original clinical plan, RapidPlan left hippocampus sparing model decreased left hippocampus mean dose by 43 % (p < 0.001), without compromising planning target volume coverage. ConclusionsIn this trial, protocol OAR constraints were appropriate for limiting grade ≥ 2 toxicities in conventional and short-course adjuvant chemoradiotherapy for glioblastoma. Higher left hippocampal mean doses were predictive for neuro-cognitive decline post-radiotherapy. Routine contouring and use of dose constraints to limit hippocampal dose is recommended to minimize neuro-cognitive decline in patients with glioblastoma treated with chemoradiotherapy.

Long-term follow-up of HER2 overexpression in patients with rectal cancer after preoperative radiotherapy: A prospective cohort study.

BACKGROUNDThe role of HER2 overexpression in rectal cancer is controversial.AIMTo assess the role of HER2 overexpression in the long-term prognosis of rectal cancer.METHODSData from patients with locally advanced rectal cancer who underwent total mesorectal excision after short-course radiotherapy at Beijing Cancer Hospital between May 2002 and October 2005 were collected. A total of 151 tissue samples of rectal cancer were obtained using rigid proctoscopy before neoadjuvant radiotherapy, followed by immunohistochemistry and fluorescence in situ hybridisation to determine the patients’ HER2 expression status. Univariate and multivariate analyses of the associations between the clinicopathological factors and HER2 status were performed. Survival was estimated and compared using the Kaplan-Meier method based on HER2 expression status, and the differences between groups were verified using the log-rank test.RESULTSA total of 151 patients were enrolled in this study. A total of 27 (17.9%) patients were ultimately confirmed to be HER2-positive. The follow-up duration ranged from 9 mo to 210 mo, with a median of 134 mo. Distant metastasis and local recurrence occurred in 60 (39.7%) and 24 (15.9%) patients, respectively. HER2 positivity was significantly associated with the pre-treatment lymph node stage (pre-N) (P = 0.040), while there were no differences between HER2 status and age, sex, preoperative CEA levels (pre-CEA), T stage, and lympho-vascular invasion. In terms of prognosis, HER2 overexpression was correlated with distant metastasis (P = 0.002) rather than local recurrence (P > 0.05). The multivariate analysis demonstrated that elevated pre-CEA [P = 0.002, odds ratio (OR) = 3.277, 97.5% confidence interval (CI): 1.543-7.163], post N(+) (P = 0.022, OR = 2.437, 97.5%CI: 1.143-5.308) and HER2(+) (P = 0.003, OR = 4.222, 97.5%CI: 1.667-11.409) were risk factors for distant metastasis. The survival analysis showed that there were significant differences between rectal cancer patients in terms of disease-free survival (DFS) [hazard ratio: 1.69 (95%CI: 0.91-3.14); P = 0.048] and overall survival (OS) [1.95 (1.05-3.63); P = 0.0077].CONCLUSIONHER2 overexpression is a potential biomarker for predicting lymph node metastasis and distant metastasis, which are associated with worse long-term DFS and OS in rectal cancer patients with locally advanced disease.

Short- and long-term outcomes in ypT2 rectal cancer patients after neoadjuvant therapy and local excision: a multicentre observational study

BackgroundAlthough local excision (LE) after neoadjuvant treatment (NT) has achieved encouraging oncological outcomes in selected patients, radical surgery still remains the rule when unfavorable pathology occurs. However, there is a risk of undertreating patients not eligible for radical surgery. The aim of this study was to evaluate the outcomes of patients with pathological incomplete response (ypT2) in a multicentre cohort of patients undergoing LE after NT and to compare them with ypT0-is-1 rectal cancers.MethodsFrom 2010 to 2019, all patients who underwent LE after NT for rectal cancer were identified from five institutional retrospective databases. After excluding 12 patients with ypT3 tumors, patients with ypT2 tumors were compared to patients with ypT0-is-1 tumors). The endpoints of the study were early postoperative and long-term oncological outcomes.ResultsA total of 177 patients (132 males, 45 females, median age 70 [IQR 16] years) underwent LE following NT. There were 46 ypT2 patients (39 males, 7 females, median age 72 [IQR 18.25] years) and 119 ypT0-is-1 patients (83 males, 36 females, median age 69 [IQR 15] years). Patients with pathological incomplete response (ypT2) were frailer than the ypT0-is-1 patients (mean Charlson Comorbidity Index 6.15 ± 2.43 vs. 5.29 ± 1.99; p = 0.02) and there was a significant difference in the type of NT used for the two groups (long- course radiotherapy: 100 (84%) vs. 23 (63%), p = 0.006; short-course radiotherapy: 19 (16%) vs. 17 (37%), p = 0.006). The postoperative rectal bleeding rate (13% vs. 1.7%; p = 0.008), readmission rate (10.9% vs. 0.8%; p = 0.008) and R1 resection rate (8.7% vs. 0; p = 0.008) was significantly higher in the ypT2 group. Recurrence rates were comparable between groups (5% vs. 13%; p = 0.15). Five-year overall survival was 91.3% and 94.9% in the ypT2 and ypT0-is-1 groups, respectively (p = 0.39), while 5-year cancer specific survival was 93.4% in the ypT2 group and 94.9% in the ypT0-is-1 group (p = 0.70). No difference was found in terms of 5-year local recurrence free-survival (p = 0.18) and 5-year distant recurrence free-survival (p = 0.37).ConclusionsPatients with ypT2 tumors after NT and LE have a higher risk of late-onset rectal bleeding and positive resection margins than patients with complete or near complete response. However, long-term recurrence rates and survival seem comparable.

Radiation Therapy Exacerbates Tumor-Promoting Innervation and Nerve Signaling in Rectal Cancer

Many solid tumors present with perineural invasion (PNI), and innervation correlates with worsened prognosis. The effects that commonly administered therapies such as radiation therapy (RT) have on PNI status remain unknown. We investigated the contribution of RT on the nervous system and elucidated the implications that increased nerve signaling can have on tumor burden using our previously developed orthotopic murine model of rectal cancer (RC) and our targeted and clinically relevant short-course RT (SCRT) regimen. Medical charts for patients with RC treated at the Wilmot Cancer Institute were obtained and PNI status was analyzed. Human data were accompanied by an orthotopic murine model of RC. Briefly, luciferase-expressing murine colon-38 (MC38-luc) tumor cells were injected orthotopically into the rectal wall of C57BL6 mice. Targeted SCRT (5 gray (Gy) per fraction for 5 consecutive fractions) was administered to the tumor. Intratumoral innervation was determined by immunohistochemistry (IHC), local norepinephrine (NE) concentration was quantified by enzyme-linked immunosorbent assay (ELISA), and β2-adrenergic receptor (B2AR) expression was assessed by flow cytometry. Chronic NE signaling was mirrored by daily isoproterenol treatment, and the effect on tumor burden was determined by overall survival, presence of metastatic lesions, and tumor size. Isoproterenol signaling was inhibited by administration of propranolol. Human RC patients with PNI have decreased overall survival compared with patients without PNI. In our mouse model, SCRT induced the expression of genes involved in neurogenesis, increased local NE secretion, and upregulated B2AR expression. Treating mice with isoproterenol resulted in decreased overall survival, increased rate of metastasis, and reduced SCRT efficacy. Interestingly, the isoproterenol-induced decrease in SCRT efficacy could be abrogated by blocking the BAR through the use of propranolol, suggesting a direct role of BAR stimulation on impairing SCRT responses. Our results indicate that while SCRT is a valuable treatment, it is accompanied by adverse effects on the nervous system that may impede the efficacy of therapy and promote tumor burden. Therefore, we could speculate that therapies aimed at targeting this signaling cascade or impairing nerve growth in combination with SCRT may prove beneficial in future cancer treatment.

Downstaging in Advanced Rectal Cancers: A Propensity-Matched Comparison Between Short-Course Radiotherapy Followed by Chemotherapy and Long-Course Chemoradiotherapy.

Short-course radiotherapy followed by chemotherapy has not been widely evaluated as an alternative to traditional long-course chemoradiotherapy in locally advanced rectal cancer. This study compared the oncological and short-term outcomes between short-course radiotherapy + chemotherapy and long-course chemoradiotherapy in locally advanced rectal cancer. This is a retrospective propensity-matched study. The study was conducted in a colorectal department at a tertiary care oncology center in India. There were 173 patients. Group A had 47 patients and group B had 126 patients. A 1:2.7 matching was done for age, sex, distance of tumor from the anal verge, sphincter preservation surgeries, MRI-based pretreatment T stage, and circumferential resection margin. The interventions performed were short-course radiotherapy + chemotherapy (group A) and long-course chemoradiotherapy (group B) in locally advanced rectal cancer. The primary measures were pathological circumferential resection margin positivity, downstaging, tumor regression grade, and postoperative complications. Of the patients, 52% had a positive circumferential resection margin on MRI, 57% had low rectal tumors, and 20% had T4 tumors. Distribution of rectal surgeries was similar between the 2 groups. pT downstaging and tumor regression scores were significantly better in group B ( p = 0.028 and 0.026). Pathological circumferential resection margin, distal resection margin, and nodal yield were similar. On multivariate analysis, pretreatment N status was the only independent predictive factor for pathological circumferential resection margin status. Grade 3 to 4 Clavien-Dindo complications, anastomotic leak rates, and hospital stay were similar between the 2 groups. This was a retrospective study. Although propensity matching was performed, selection bias cannot be eliminated completely, as seen in the difference in the surgical approaches between the 2 groups. In a cohort containing a significant portion of MRI circumferential resection margin-positive low rectal cancers, short-course radiotherapy + chemotherapy followed by delayed surgery resulted in lower T downstaging and lower tumor regression scores compared with long-course chemoradiotherapy, but pathological circumferential margin status, distal resection margin, nodal yield, and perioperative morbidity were similar between the 2 groups. This suggests that short-course radiotherapy + chemotherapy could be a viable alternative to long-course chemoradiotherapy in locally advanced rectal cancers. See Video Abstract at http://links.lww.com/DCR/B855 . ANTECEDENTES:La radioterapia de ciclo corto seguida de quimioterapia no ha sido evaluada ampliamente como una alternativa a la tradicional quimio radioterapia de ciclo largo en el cáncer de recto localmente avanzado.OBJETIVO:Estudio que compara los resultados oncológicos y a corto plazo entre la radioterapia de ciclo corto + quimioterapia y la quimio radioterapia de ciclo largo en el cáncer de recto localmente avanzado.DISEÑO:Estudio comparado de propensión de manera retrospectiva.AJUSTE:Departamento colorrectal en un centro de atención oncológica de tipo terciario en la India.PACIENTES:Hubo 173 pacientes. El grupo A tenía 47 y el grupo B tenía 126 pacientes. Se realizó una comparación de 1: 2,7 para edad, sexo, distancia del tumor desde el margen anal, cirugías de preservación del esfínter, estadio T previo al tratamiento basada en resonancia magnética y margen de resección circunferencial (CRM).INTERVENCIONES:Radioterapia de ciclo corto + quimioterapia (grupo A) y quimio radioterapia de ciclo largo (grupo B) en cáncer de recto localmente avanzado (LARC).PRINCIPALES MEDIDAS DE RESULTADO:Positividad histopatológica de CRM, reducción del estadio tumoral, grado de regresión tumoral, complicaciones posoperatorias.RESULTADOS:El 52% de los pacientes han tenido un margen de resección circunferencial positivo en la resonancia magnética, 57% de tumores rectales bajos, 20% de tumores T4. La distribución de cirugías rectales fue similar entre los 2 grupos. Las puntuaciones de regresión tumoral y de reducción del estadio de pT fueron significativamente mejores en el grupo B ( p = 0.028 y 0.026 respectivamente). El margen de resección circunferencial patológico, el margen de resección distal y los ganglios arrojados fueron similares. En el análisis multivariado, el estadio N previo al tratamiento fue el único factor predictivo independiente para el estadio de pCRM. Las complicaciones Clavien-Dindo de grado 3-4, las tasas de fuga anastomótica y la estancia hospitalaria fueron similares entre los dos grupos.LIMITACIONES:Retrospectiva; aunque la propensión coincide, existe potencial sesgo de selección.CONCLUSIONES:En una cohorte que contenía una porción significativa de cánceres rectales bajos con margen de resección circunferencial positivo por resonancia magnética, la radioterapia de ciclo corto + quimioterapia seguida de cirugía tardía dio como resultado una mayor reducción del estadio T y de regresión tumoral en comparación con la quimio radioterapia de ciclo largo. Pero el estatus histopatológico del margen circunferencial, el margen de resección distal, el rendimiento ganglionar y la morbilidad perioperatoria fueron similares entre los dos grupos. Esto sugiere que la radioterapia de ciclo corto + quimioterapia podría ser una alternativa viable a la quimio radioterapia de ciclo largo en cánceres rectales localmente avanzados. Consulte Video Resumen en http://links.lww.com/DCR/B855 . (Traducción-Dr. Osvaldo Gauto ).

Optimal Neoadjuvant Strategies for Locally Advanced Rectal Cancer by Risk Assessment and Tumor Location

Neoadjuvant therapy is standard of care for locally advanced rectal cancer (LARC). Advancements in multimodality therapy options and sequencing of radiation therapy (RT), surgery, and chemotherapy make decision-making challenging. Traditional treatment of patients with LARC involves neoadjuvant chemoradiation followed by total mesorectal excision and consideration of adjuvant chemotherapy. Advancement in RT has led to trials offering both short-course and long-course RT with good long-term clinical outcomes. Intensification of therapy in high-risk patients has led to studies of total neoadjuvant therapy with chemotherapy and chemoradiation, now standard management for most LARC. De-escalation of therapy in patients with favorable prognosis has led to several considerations, including non-total mesorectal excision management or neoadjuvant chemotherapy only. Several considerations of patient and disease factors can help inform the optimal chemotherapy regimens in different sequencing of neoadjuvant strategies. Finally, novel biomarkers, such as microsatellite instability, has led to utilization of novel therapies, including neoadjuvant immunotherapy, with substantial response. This review attempts to frame the rapidly growing data in LARC in context of disease and patient risk factors, to inform optimal, personalized treatment of patients with LARC.

Rectal Cancer, Version 2.2022, NCCN Clinical Practice Guidelines in Oncology.

This selection from the NCCN Guidelines for Rectal Cancer focuses on management of malignant polyps and resectable nonmetastatic rectal cancer because important updates have been made to these guidelines. These recent updates include redrawing the algorithms for stage II and III disease to reflect new data supporting the increasingly prominent role of total neoadjuvant therapy, expanded recommendations for short-course radiation therapy techniques, and new recommendations for a "watch-and-wait" nonoperative management technique for patients with cancer that shows a complete response to neoadjuvant therapy. The complete version of the NCCN Guidelines for Rectal Cancer, available online at NCCN.org, covers additional topics including risk assessment, pathology and staging, management of metastatic disease, posttreatment surveillance, treatment of recurrent disease, and survivorship.

Patient- and physician-reported radiation-induced toxicity of short-course radiotherapy with a prolonged interval to surgery for rectal cancer.

A prolonged interval (>4 weeks) between short-course radiotherapy (25 Gy in five fractions) (SCRT-delay) and total mesorectal excision for rectal cancer has been associated with a decreased postoperative complication rate and offers the possibility of organ preservation in the case of a complete tumour response. This prospective cohort study systematically evaluated patient-reported bowel dysfunction and physician-reported radiation-induced toxicity for 8 weeks following SCRT-delay. Patients who were referred for SCRT-delay for intermediate risk, oligometastatic or locally advanced rectal cancer were included. Repeated measurements were done for patient-reported bowel dysfunction (measured by the low anterior resection syndrome [LARS] questionnaire and categorized as no, minor or major LARS) and physician-reported radiation-induced toxicity (according to Common Terminology Criteria for Adverse Events version 4.0) before start of treatment (baseline), at completion of SCRT and 1, 2, 3, 4, 6 and 8 weeks thereafter. Fifty-one patients were included; 31 (61%) were men and the median age was 67 years (range 44-91). Patient-reported bowel dysfunction and physician-reported radiation-induced toxicity peaked at weeks 1-2 after completion of SCRT and gradually declined thereafter. Major LARS was reported by 44 patients (92%) at some time during SCRT-delay. Grade 3 radiation-induced toxicity was reported in 17 patients (33%) and concerned predominantly diarrhoea. No Grade 4-5 radiation-induced toxicity occurred. During SCRT-delay, almost every patient experiences temporary mild-moderate radiation-induced toxicity and major LARS, but life-threatening toxicity is rare. SCRT-delay is a safe alternative to SCRT-direct surgery that should be proposed when counselling rectal cancer patients on neoadjuvant strategies.

The Impact of Postoperative Complications on Short- and Long-Term Health-Related Quality of Life After Total Mesorectal Excision for Rectal Cancer

BackgroundSurvival for rectal cancer patients has improved over the past decades. In parallel, long-term health-related quality of life (HRQoL) is gaining interest. This study focuses on the effect of complications following rectal cancer surgery on HRQoL and survival. MethodsThe TME-trial (1996-1999) randomized patients with operable rectal cancer between surgery with preoperative short-course radiotherapy and surgery. Questionnaires including the Rotterdam Symptom Checklist were sent at 6 time points within the first 24 months and after 14 years the EORTC QLQ-C30 and EORTC QLQ-CR29 questionnaires. Differences in HRQoL and survival between patients with and without complications were analyzed. ResultsA total of 1207 patients were included, of which 482 (39.9%) patients experienced complications, surgical complications occurred in 177 (14.6%) patients, non-surgical complications in 197 (16.3%) and 108 patients (8.9%) had a combination of both types of complications. Three months after surgery, patients with a combination of surgical- and non-surgical complications, especially patients with anastomotic leakage, had the worst HRQoL. Twelve months postoperative HRQoL returned to a similar level as before surgery, regardless of complications. In patients who survived 14 years, no significant differences in HRQoL were seen between patients with and without complications. However, patients with complications did have lower overall survival. ConclusionThis study shows that survival and short-term HRQoL are negatively affected by complications. Twelve months after surgery HRQoL had returned to the preoperative level regardless, of complications. Also, in patients that survived 14 years, there was no effect of complications on HRQoL detected.

Current Practice Patterns in Locally Advanced Rectal Cancer at Academic Institutions: A National Survey Among Radiation Oncologists, Medical Oncologists, and Colorectal Surgeons

PurposeTo assess the current treatment patterns in locally advanced rectal cancer (LARC) among radiation oncologists (RO), medical oncologists (MO), and colorectal surgeons (SR) specializing in gastrointestinal (GI) malignancies at academic institutions. Materials and MethodsAn online survey consisting of 7 LARC clinical vignettes was distributed to GI specialists practicing at ACGME accredited academic institutions. Treatment paradigms consisted of long-course chemoradiation (LC-CRT) and short-course (SCRT) radiotherapy, chemotherapy (CHT), and surgery. The survey was open from January to April 2021. ResultsThirty-six RO, 14 MO and 21 SR (71/508 physicians) replied resulting in a response rate of 14.0%. For low rectal node positive tumors, 88.7% of primary recommendations incorporated TNT (73.1% LC-CRT, 26.9% SCRT). NOM was preferred by 41.3% if a clinical complete response (cCR) was achieved. The presence of high-risk features led 95.8% of physicians to employ TNT (79.4% LC-CRT, 20.6% SCRT). For a cT3N1-2 mid-rectal tumor without high-risk features, 85.9% would primarily recommend TNT (56.6% LC-CRT, 43.4% SCRT). For a cT4bN2a mid-rectal tumor without high-risk features, 97.2% of primary recommendations included TNT (76.9% LC-CRT, 23.1% SCRT). ConclusionAmong academic RO, MO, and SR, the traditional regimen of LC-CRT, surgery, and adjuvant CHT is now infrequently recommended for LARC. TNT has been widely adopted for locally advanced node positive rectal tumors with variable patterns of care with respect to sequencing of CHT and RT. Fractionation with LC-CRT remained the majority. Non-operative management after a cCR in low rectal tumors has gained traction transforming LARC from a once classically perceived surgical disease.

The Evolving Landscape of Immunotherapy in Locally Advanced Rectal Cancer Patients

Simple SummaryAt the last 2022 annual ASCO meeting, impressive results of anti-PD1 activity in clinical stage 2 and 3 microsatellite instable rectal cancer patients have been published. Moreover, a growing number of studies assessed the synergism between neoadjuvant (chemo)radiotherapy and immunotherapy in microsatellite stable localized rectal cancer patients. Major findings of immunotherapy activity and efficacy in localized rectal cancer, according to microsatellite status, are discussed in this commentary.Standard treatments of localized rectal cancer are surgery or the multimodal approach with neoadjuvant treatments (chemo-radiotherapy, short-course radiotherapy, induction, or consolidation chemotherapy) followed by surgery. In metastatic colorectal cancer (mCRC), immune checkpoint inhibitors (ICIs) are now the first choice in patients with a deficient mismatch repair system/microsatellite instability (dMMR/MSI-H) and are being explored in combination with chemotherapy to rewire the immune system against malignant cells in subjects with proficient mismatch repair system/microsatellite low (pMMR/MSI-L) cancers, with promising signals of efficacy. Recently, some efforts have been made to translate ICIs in earlier stages of CRC, including localized rectal cancer, with breakthrough efficacy and an organ preservation rate of mono-immunotherapy in dMMR/MSI-H patients and promising anti-tumor activity of immunotherapy plus neoadjuvant (chemo)radiotherapy in pMMR/MSI-L subjects. Here, we present the rationale, results, and limitations of the most remarkable trials assessing ICIs in dMMR/MSI-H and pMMR/MSI-L localized rectal cancer patients, at the same time highlighting the most promising research perspectives that have followed these studies.

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.

Three perspectives: the approach to neoadjuvant treatment of rectal cancer according to medical oncologists, radiation oncologists, and surgeons

Background: Two treatment options considered for radiotherapy are short-course radiotherapy and immediate surgery, or chemoradiation with 5-Fluorouracil based chemotherapy and delayed surgery. Aim of the study: Evaluate the real-life treatment approaches of medical, radiation, and surgical oncologists, to neoadjuvant treatment of rectal cancers. Material and methods: An online survey was established via Google Forms. The survey was taken voluntarily by medical oncologists, radiation oncologists, surgical oncologists, and general surgeons. Results: Of those who participated, 183 were medical oncologists, 36 were radiotherapists, and 36 were surgeons. Most of the study population preferred long-course radiation therapy and chemotherapy (85%). Meanwhile, two-thirds of the participants preferred chemotherapy prior to operating. The most frequent chemotherapy cycles for the pre-operative setting were ‘three’ and ‘four-or-more’ (27.8% and 25.1%, respectively). Medical oncologists had a significantly higher tendency to offer chemotherapy between radiation therapy and surgery compared to the other groups. Optimal time of surgery was different between groups, but there was no difference among groups between surgery and the ‘watch &amp; wait’ strategy. Neoadjuvant chemotherapy regimens were significantly different between groups. Conclusions: We found that the new pre-operative chemotherapy regimen with short-course radiotherapy was slowly adopted into current practice. Also, medical oncologists tended to prefer pre-operative chemotherapy in comparison to the other groups.

P11.72.A Glioblastoma in elderly patients. Which is the best treatment option?

Abstract Background Glioblastoma (GBM) is the most common and aggressive primary malignant brain tumor in adults, and it is associated with a poor prognosis in the elderly. The current standard of care for newly diagnosed GBM is maximal surgical resection, followed by radiotherapy plus concomitant and adjuvant temozolomide (TMZ). In elderly patients with GBM, short-courses of radiotherapy with TMZ are used. Material and Methods We performed a single-center retrospective analysis of elderly GBM patients treated from 2013 to 2020. The primary endpoint was to evaluate progression free survival (PFS) and overall survival (OS) according to treatment received (TMZ and standard radiotherapy (60 Gy over a period of 6 weeks) vs TMZ and short-course radiotherapy (40 Gy in 15 fractions)). Secondary endpoints were analysis of population demographics and major toxicities associated to treatment. Results Twenty-two patients were identified. The median age was 72 years (range 65- 80), 18 (85.7%) patients were in ECOG-PS 0-1, 12 (57.1%) were males and all patients had undergone partial or complete resection surgery. Eleven (52.4%) patients received TMZ and standard radiotherapy and 10 (47.6%) patients received TMZ and short-course radiotherapy. Three (14.3%) patients had complete remission, 11 (52.4%) patients had partial response, 2 (9.5%) patients presented stable disease and 5 (23.8%) patients had disease progression. Median OS was 9 months (95% CI, 3.6 to 14.4) with TMZ with standard radiotherapy and 8 months (95% CI, 1.8 to 14.2) with TMZ and short-course radiotherapy (p=0.322). Median PFS was 5 months (95% CI, 2.8 to 7.2) with TMZ with standard radiotherapy and 6 months (95% CI, 3.1 to 8.9) with TMZ and short-course radiotherapy (p=0.944). Most common toxicities were hematological, with 5 (23.8%) patients presented thrombocytopenia grade 2 or higher. Five (23.8%) patients presented grade 3/4 toxicities (2 (9.5%) patients presented thrombocytopenia grade 4, 1 (4.8%) patient presented thrombocytopenia grade 3, and 2 (9.5%) patients presented anemia grade 3. Conclusion The prognosis of GBM remains poor besides standard therapy. TMZ and short-course radiotherapy should be an option in elderly patients due to its non-inferiority. Elderly patients should undergo a careful geriatric evaluation before starting treatment.

30: Statin Therapy in Patients Undergoing Short-Course Neoadjuvant Radiotherapy for Rectal Cancer

30: Statin Therapy in Patients Undergoing Short-Course Neoadjuvant Radiotherapy for Rectal Cancer

10: Cost Minimization Analysis of Conventional Versus Short-Course Radiotherapy with Temozolomide for Non-Elderly Patients with Newly Diagnosed Glioblastoma

10: Cost Minimization Analysis of Conventional Versus Short-Course Radiotherapy with Temozolomide for Non-Elderly Patients with Newly Diagnosed Glioblastoma

430P Prediction of pathologic complete response to preoperative (chemo)radiotherapy and/or chemotherapy in rectal cancer using clinical and imaging parameters

Complete pathological response (pCR) is achieved in 10-20% of rectal cancers when treated with preoperative short-course radiotherapy (scRT) or long-course chemoradiotherapy (CRT) and in 28% with total neoadjuvant therapy (TNT) including scRT/CRT with chemotherapy. pCR is linked to better outcome. Which clinical or imaging factors predict pCR?.