Preoperative Hypofractionated Radiotherapy Research Articles

Treatment Outcome in Locally Advanced Rectal Carcinoma and Its Correlation with Hypo-Fractionated Radiotherapy and Concurrent Chemoradiotherapy

Introduction: Rectal cancer is the second most common type within the large intestine, posing significant health risks globally. In Bangladesh, it ranks high among diagnosed cancers. Improved diagnostic methods aid in early detection, which is crucial for effective management. Treatment typically involves a combination of surgery, radiotherapy, and chemotherapy. Preoperative chemoradiotherapy is a standard approach. However, newer methods like preoperative hypo-fractionated radiotherapy with surgery promise better outcomes, including reduced recurrence rates and enhanced survival, with potential cost and time savings. Aim of the Study: The study aims to evaluate and contrast the efficacy of hypofractionated radiotherapy and concurrent chemoradiotherapy in patients with locally advanced rectal carcinoma. Methods: The study, conducted at the Department of Clinical Oncology at Bangabandhu Sheikh Mujib Medical University Shahbagh, Dhaka, Bangladesh and the Department of Radiation Oncology at the National Institute of Cancer Research and Hospital (NICR&H) in Mohakhali, Dhaka, Bangladesh, aimed to compare treatments for locally advanced rectal cancer over 1.5 years (From January 2018 to June 2019). A total of 80 patients were divided into two groups; Group A received hypofractionated radiotherapy, while Group B received oral capecitabine alongside external beam radiotherapy. Inclusion criteria involved confirmed adenocarcinoma within specified stages, with ethical clearances obtained. Patients underwent evaluations before treatment and response assessments posttreatment. Treatment modalities were defined, focusing on radiotherapy and chemotherapy. Data were analyzed using SPSS software, employing various statistical tests. Results aimed to address study objectives while minimizing biases. Result: The study involved 80 patients, divided into Groups A and B, each with 40 individuals. Group A mainly comprised individuals aged 41-50 (45%), followed by 31-40 (25%). Group B had the highest proportion aged 31-40 (30%) and 41-50 (32.50%). Both groups showed male predominance (1.3:1). Moderately differentiated tumors were common, with Group A having more poorly differentiated tumors. Stage III was predominant pre-treatment (65% Group A, 70% Group B). Most patients presented with per rectal bleeding (80%) and alteration of bowel habits (56.25%). Response rates to treatment were similar between groups. Tumor downsizing was more frequent in Group B. Sphincter-sparing surgery was feasible in both groups with no significant difference. Conclusion: The study comparing preoperative hypofractionated radiotherapy (RT) to concurrent chemoradiotherapy (CCRT) for locally advanced rectal carcinoma found similar efficacy in tumor response, downsizing, and sphincter preservation. Statistical analysis showed no significant differences. Both approaches showed acceptable short-term outcomes, offering clinicians options based on patient and resource considerations.

Neutrophil-to-lymphocyte ratio for the prediction of soft tissue sarcomas response to pre-operative radiation therapy

Purpose/ObjectiveThis study aims to assess the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) in soft tissue sarcomas (STS) treated with pre-operative hypofractionated radiotherapy (HFRT). Materials/MethodsThis retrospective analysis included patients treated with pre-operative HFRT of 30 Gy in 5 fractions between 2016 and 2023. Clinical, demographic, and complete blood count (CBC) data were collected. NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. Only patients with CBCs conducted within 6 months after radiotherapy were included. Cox proportional-hazard regression models were used to assess the impact of NLR and different variables on outcomes. Kaplan Meier were used to illustrate survival curves. A p-value < 0.05 was considered significant, and 95 % confidence intervals (CI) were employed. ResultsA total of 40 patients received HFRT and had CBCs within 6 months after radiotherapy. There were 17 (42.5 %) females and 23 (57.5 %) males with a mean age of 66 years. The mean largest tumor size dimension was 7.1 cm, and the mean NLR post-RT was 5.3. The most frequent histological subtypes were myxofibrosarcoma (17.5 %), pleomorphic spindle cell sarcoma (10 %), leiomyosarcoma (7.5 %), and myxoid liposarcoma (5 %). The median follow-up period was 15.4 months. From all patients, 14 patients had disease progression, 12 metastatic disease and 3 died of disease. Multivariable Cox proportional-hazards regression analysis displayed that a higher post-RT NLR was associated with worse disease-free survival (DFS) (HR: 1.303 [1.098–1.548], p = 0.003), and distant metastasis-free survival (DMFS) (HR: 1.38 [1.115–1.710], p = 0.003). Moreover, post-NLR ≥ 4 as a single variable was associated with worse DFS, DMFS, but not worse local recurrence or overall survival. ConclusionThis study is the first to evaluate NLR as a prognostic biomarker in STS patients treated with pre-operative radiotherapy. A higher NLR after pre-operative radiotherapy was associated with increased disease progression.

Postoperative complications following neoadjuvant therapy and surgery in a phase 2 borderline resectable pancreatic cancer clinical trial (Alliance A021501).

664 Background: Postoperative complications in patients with borderline resectable pancreatic cancer treated with neoadjuvant therapy and pancreatectomy in the national cooperative group setting have not been previously characterized. Further, the impact of preoperative hypofractionated radiotherapy on postoperative outcomes is largely unknown. We sought to quantify perioperative morbidity among patients with pancreatic cancer who received neoadjuvant modified FOLFIRINOX chemotherapy with or without hypofractionated radiotherapy on a multicenter clinical trial. Methods: The A021501 phase 2 trial randomized patients with borderline resectable pancreatic ductal adenocarcinoma to 8 doses of mFOLFIRINOX (Arm 1) or 7 doses of mFOLFIRINOX then hypofractionated radiotherapy (Arm 2), followed by pancreatectomy (Dec 31, 2016-Jan 1, 2019). Patients underwent resection according to defined operative standards at enrolling centers without specific requirements for either surgeon or hospital volume. Surgical complications and adverse events were assessed and captured at a single time point of 90 days after surgery and compared between treatment arms. Results: Of 126 enrolled patients, 51 (40%) underwent pancreatectomy (n=32, Arm 1; n=19, Arm 2) at 28 institutions. Vascular resection was performed in 19 patients (37%). One patient in Arm 2 died within 90 days after surgery. Rates of any surgical complication were 19% (n=6) in Arm 1 and 42% (n=8) in Arm 2 (p=0.07). Median length of stay was 7 days (range 5-38 days). Five (10%) patients required reoperation within 90 days. Readmission rates were higher in Arm 2 than Arm 1 (16% vs. 42%, p=0.04) but there were no differences in rates of reoperation, pancreatic fistula or abscess requiring drainage, or wound infection between study arms. 54% of patients (n=26/48) experienced a grade 3 or higher adverse event, with no difference between treatment arms (47% versus 67%, p=0.7). Rates of initiation of adjuvant therapy did not differ between treatment arms (66% vs. 68%, p=0.4). Pancreatic fistula and abscess were associated with adjuvant therapy (p&lt;0.01). No difference in overall survival was observed based on occurrence of surgical complications (HR 1.1; 95% CI 0.5-2.6). Conclusions: In this national cooperative group study of patients with borderline resectable pancreatic cancer,postoperative complications following neoadjuvant chemotherapy, radiation, and surgical resection were consistent with rates previously reported by high-volume institutions and using large datasets. Multimodality trials of preoperative therapy for locoregionally advanced pancreatic cancer may be safely performed in the cooperative group setting. Clinical trial information: NCT02839343 .

Post-Hypofractionated Radiotherapy Neutrophil-to-Lymphocyte Ratio in Soft Tissue Sarcomas is a Prognostic Biomarker of Recurrence and Distant Metastases

The neutrophil-to-lymphocyte ratio (NLR) is a measure of systemic inflammation, and known to be prognostic of outcomes and treatment response across different cancer types, including soft tissue sarcomas (STS). Our study aims to determine if in patients with STS treated with pre-operative hypofractionated radiotherapy (HFRT), post-RT NLR is prognostic of recurrence, metastasis, and overall survival. We performed a single-center retrospective analysis of patients treated pre-operatively with 30 Gy in 5 fractions between 2016 and 2023. Clinical, demographic, radiation therapy (RT), and complete blood count (CBC) data were collected from medical records. The NLR calculation was performed by dividing the absolute neutrophils count by the absolute lymphocytes count. We dichotomized the variable into NLR ≤4 and >4. The CBC utilized to calculate NLR was only used if done <6 months post-RT. For post-RT NLR outcomes associations, we used univariable and multivariable logistic regression analyses adjusting for age, gender, tumor size, and histology. For continuous variables we used mean ± standard deviation. Analyses were done with SPSS. A p-value <0.05 was considered significant. We identified 40 patients that received HFRT and had a CBC within 6 months after RT. The mean age was 66 ± 17.5 years. There were 17 (42.5%) females and 23 (57.5%) males. The histologies were myxofibrosarcoma (17.5%), leiomyosarcoma (7.5%), pleomorphic spindle cell sarcoma (10%), myxoid liposarcoma (5%). Other histologies with n<2 accounted for 65%. The mean tumor size was 7.1cm (± 6.4) and the mean NLR 5.3 ± 0.6. The median follow-up was 15.4 ±2.2 months. The patients with recurrence and metastases were the same {n = 13 (32.5%)}, and 3 patients died of disease. Univariable analyses for NLR > 4 showed increased recurrence and metastases (Odds ratio (OR): 8, CI 95% = {1.48 - 43.4}, p = 0.016). The multivariable analyses also showed that post-RT NLR > 4, was associated with increased recurrence and metastases (OR: 7.73, CI 95% = {1.17- 50.9}, p- value = 0.034). Age, gender, histology, and tumor size were not significant variables (Table 1). In both univariable and multivariable analyses NLR > 4 was not associated with decreased overall survival (p = 0.998). To our knowledge, this is the first study assessing the immune response using neutrophil-to-lymphocyte ratio as a prognostic biomarker in STS treated with pre-operative hypofractionated radiotherapy. In this population, an NLR > 4 was prognostic for recurrence and distant metastasis, but not for overall survival. This study highlights the need for a better understanding of the immuno-biological effects of RT, which should be further addressed in the context of clinical trials due to its simplicity and potential prognostic value.

Preoperative hypofractionated radiotherapy for soft tissue sarcoma.

In The Lancet Oncology, B Ashleigh Guadagnolo and colleagues1 report the early results of a single-arm, single-centre, prospective trial (HYPORT-STS) evaluating a moderately hypofractionated regimen of preoperative radiotherapy (42·75 Gy in 15 fractions of 2·85 Gy/day for 3 weeks [five fractions per week]) in patients with soft tissue sarcomas of the extremities or trunk. The authors chose the landmark CAN-NCIC-SR2 trial2,3 for comparison in the absence of randomisation and strictly defined their primary endpoint of major wound complications within 120 days of surgery consistently with the comparative trial.

Efficacy and Safety of Hypofractionated Preoperative Radiotherapy for Primary Locally Advanced Soft Tissue Sarcomas of Limbs or Trunk Wall.

Simple SummaryThe primary treatment of soft tissue sarcomas (STS) is radical resection. The use of adjuvant radiotherapy showed a significantly decreased incidence of local recurrence. In our previous study, we presented that preoperative hypofractionated radiotherapy is safe and efficient for treating an unselected group of patients with STS. This study aimed to assess the treatment scheme’s use in patients with primary STS treated at one institution. The preoperative radiotherapy (RT) scheme consisted of 5 Gy per fraction for a total dose of 25 Gy. Surgery was performed within 2–4 days from the last day of RT. We included 311 patients in this prospective study. In this group, with a significant percentage of patients with extensive, high-grade STS, hypofractionated preoperative radiotherapy was associated with similar local control compared to published studies dedicated to this population. The early tolerance was good, with a small number of late complications. Background: The use of adjuvant radiotherapy (RT) shows a significantly decreased incidence of local recurrence (LR) in soft tissue sarcomas (STS). This study aimed to assess the treatment scheme’s effect in patients with primary STS treated at one institution. Methods: In this phase 2 trial, 311 patients aged ≥18 years with primary, locally advanced STS of the extremity or trunk wall were assigned to multimodal therapy conducted at one institution. The preoperative RT scheme consisted of 5 Gy per fraction for a total dose of 25 Gy. Surgery was performed within 2–4 days from the last day of RT. The primary endpoint was LR-free survival (LRFS). Adverse events of the treatment were assessed. Results: We included 311 patients with primary locally advanced STS. The median tumor size was 11 cm. In total, 258 patients (83%) had high-grade tumors. In 260 patients (83.6%), clear surgical margins (R0) were obtained. Ninety-six patients (30.8%) had at least one type of treatment adverse event. LR was observed in 13.8% patients. The 5-year overall survival was 63%. Conclusion: In this group, with a significant percentage of patients with extensive, high-grade STS, hypofractionated preoperative RT was associated with good local control and tolerance.

OC-0087: Preoperative Hypofractionated Radiation Therapy for Soft Tissue Sarcomas of Extremity and Trunk

OC-0087: Preoperative Hypofractionated Radiation Therapy for Soft Tissue Sarcomas of Extremity and Trunk

Treatment effect prediction for sarcoma patients treated with preoperative radiotherapy using radiomics features from longitudinal diffusion-weighted MRIs

The objective of this study was to explore radiomics features from longitudinal diffusion-weighted MRIs (DWIs) for pathologic treatment effect prediction in patients with localized soft tissue sarcoma (STS) undergoing hypofractionated preoperative radiotherapy (RT). Thirty patients with localized STS treated with preoperative hypofractionated RT were recruited to this longitudinal imaging study. DWIs were acquired at three time points using a 0.35 T MRI-guided radiotherapy system. Treatment effect score (TES) was obtained from the post-surgery pathology as a surrogate of treatment outcome. Patients were divided into two groups based on TES. Response prediction was first performed using a support vector machine (SVM) with only mean apparent diffusion coefficient (ADC) or delta ADC to serve as the benchmark. Radiomics features were then extracted from tumor ADC maps at each of the three time points. Logistic regression and SVM were constructed to predict the TES group using features selected by univariate analysis and sequential forward selection. Classification performance using SVM with features from different time points and with or without delta radiomics were evaluated. Prediction performance using only mean ADC or delta ADC was poor (area under the curve (AUC) < 0.7). For the radiomics study using features from all time points and corresponding delta radiomics, SVM significantly outperformed logistic regression (AUC of 0.91 ± 0.05 v.s. 0.85 ± 0.06). Prediction AUC values using single or multiple time points without delta radiomics were all below 0.74. Including delta radiomics of mid- or post-treatment relative to the baseline drastically boosted the prediction. In this work, an SVM model was built to predict the TES using radiomics features from longitudinal DWI. Based on this study, we found that use of mean ADC, delta ADC, or radiomics features alone was not sufficient for response prediction, and including delta radiomics features of mid- or post-treatment relative to the baseline can optimize the prediction of TES, a pathologic and clinical endpoint.

Hypofractionated Radiotherapy in Locally Advanced Myxoid Liposarcomas of Extremities or Trunk Wall: Results of a Single-Arm Prospective Clinical Trial.

Introduction: Myxoid liposarcoma (MLPS) has been reported to be more radiosensitive compared with other soft tissue sarcomas. The main objective of the study was to assess the efficacy of hypofractionated radiotherapy (RT) in the preoperative setting in patients with locally advanced primary MLPS. Methods: Single-arm prospective exploratory clinical trial enrolled MLPS patients for preoperative 5 × 5 Gy RT with delayed surgery. The endpoints of the study were the rate of early wound healing complications and 5-year local control rate. Results: 29 patients (pts) were included, all had tumors located on the lower limb. The median maximum size of the tumor was 13 cm (IQR 10–15 cm). Early RT tolerance was good. Postoperative wound complications occurred in 11 pts (37.9%), late complications concerned 13.8% of patients. A total of 27 patients were included for the efficacy analyses. The pathological features of response to RT were detected in all analyzed surgical specimens. In 25 patients R0 margins were achieved, two patients had an R1 resection. None of the patients had local recurrence. Conclusion: Preoperative hypofractionated RT with a prolonged gap between RT and surgery is a feasible method of the management of MLPS, providing a good local control and low rates of treatment toxicity.

Early Outcomes of Preoperative 5-Fraction Radiation Therapy for Soft Tissue Sarcoma Followed by Immediate Surgical Resection

PurposeThere are limited data regarding the use of hypofractionated radiation therapy (RT) for soft tissue sarcoma. We report early oncologic outcomes and wound complications of patients undergoing preoperative hypofractionated (5 fraction) RT followed by immediate surgical resection. Methods and MaterialsAn institutional review board–approved database of patients treated with preoperative RT for soft tissue sarcoma was queried. Patients treated with a hypofractionated dosing regimen followed by immediate (within 7 days) planned wide surgical resection were identified. ResultsBetween 2016 and 2019, 16 patients met eligibility criteria. The median patient age was 64 years old (range, 33-88). Ten of the sarcomas were located in the lower extremity, 4 in the upper extremity, and 2 were located in the trunk. Four patients had metastatic disease at diagnosis. The majority of the patients received a total radiation dose of 30 Gy in 5 fractions (range, 27.5-40 Gy) on consecutive days. All patients were planned with intensity modulated radiation therapy or volumetric arc therapy. The median time to surgical resection after the completion of RT was 1 day (range, 0-7 days). The median time from initial biopsy results to completion of primary oncologic therapy was 20 days (range, 16-35). Ten patients achieved R0 resection, whereas the remaining 6 patients achieved R1 resection. Of the 13 patients assessed for local control, no patients developed local failure. Within the median follow-up time of 10.7 months (range, 1.7-33.2), 5 patients developed wound healing complications (31%), of which only 3 patients (19%) required return to the operating room. ConclusionsTreatment of soft tissue sarcoma with preoperative hypofractionated RT followed by immediate resection resulted in a median of 20 days from biopsy results to completion of oncologic therapy. Early outcomes demonstrate favorable wound healing. Further prospective data with long-term follow-up is required to determine the oncologic outcomes and toxicity of hypofractionated preoperative RT.

Efficacy and safety of hypofractionated preoperative radiotherapy in treatment of patient with primary locally advanced soft tissue sarcoma of limbs/trunk wall.

11555 Background: Soft tissue sarcomas (STS) are rare often malignant tumors. The primary treatment of most STS is radical resection with adjuvant radiotherapy. Our previous study showed that the use of preoperative hypofractionated radiotherapy is safe and efficient in the treatment of unselected group of patients with STS. Aim of this study was to assess the use of the treatment scheme in patients with primary STS treated in one institution. Methods: 311 patients (52% female) with primary locally advanced STS participated in this prospective trial conducted from 2010 till 2017. Median age was 55 years (range: 17-91). Median follow up is 57 months (95%CI 55-61). The most common subtypes were pleomorphic sarcoma, liposarcoma and synovial sarcoma. Median tumor size was 11cm. 258 patients (83%) had high grade tumors. The most common tumor localization were lower limbs (72%). 30% of patients received preoperative chemotherapy. For five consecutive days radiotherapy in 5 x 5Gy fraction was applied, with immediate (2-4 days) resection of the tumor. Results: In 260 patients (83.6%) clear surgical margins (R0) were obtained. 107 patients were dead at the time of the analysis.5-year overall survival is 63%. 156 (50%) had a recurrence of the disease. Local recurrence (LR) was found in 13.8% of the patients. Median time from surgery to LR was 14.7 months. In 56% of patients with LR another limb spearing radical surgery could be performed. Factors that had a significant adverse impact on LR were histological subtype (p = 0.017) and surgical margin status (p = 0.013). Factors that had a significant adverse impact on overall survival were tumor size (p &lt; 0.0001), grade (p = 0.0047) and surgical margin status (p = 0.013). 96 patients (30.8%) had any kind of treatment toxicity, factor having negative impact on the toxicity was lower limb location of the tumor (p = 0.0012). 20 patients (6.4%) required surgery for treatment of the complications. 14.6% patients had prolonged healing of the wound ( &gt; 1 month), 8.3% had wound dehiscence, 1.4% required prolonged punctures of the lymph fluid, 2.3% had severe fibrosis leading to contracture of limb, 11% patients prolonged edema of the operated limb. 0.9% of patients had a fracture of the treated limb. Conclusions: In this group, with a big percentage of patients with large, high grade STS use of hypofractionated preoperative radiotherapy was associated with similar local control when compared to published studies. The early toxicity is tolerable, with a small amount of late complications.

Does Preoperative Hypofractionated Radiation Therapy for Soft Tissue Sarcoma Impact Post-operative Wound Complications?

Standard treatment for soft tissue sarcoma (STS) includes conventionally fractionated radiotherapy at 1.8-2 Gy/fx followed by surgical resection resulting in wound complication rates of 35% (O’Sullivan et al., Lancet 2002). STS has a low α/β ratio suggesting higher doses per fraction should lead to improved tumor control with a similar side effect profile. This single arm phase 2 clinical trial assessed the safety of preoperative hypofractionated radiotherapy in patients with STS. Patients with newly diagnosed and histologically confirmed Stage I-III STS of the extremity or chest wall were enrolled on this protocol at one institution. Patients were deemed resectable with negative margins and treated with radiotherapy to 3500 cGy in 5 fractions administered every other day prior to undergoing resection 4 to 6 weeks after completion of treatment. The primary outcome was wound complications assessed using the NCIC definition. Secondary outcomes included local control, disease free survival, and overall survival. Twenty-six patients enrolled with 24 completing surgical resection. Of these patients, 14 were male and 10 female and the median age was 66. Median tumor size was 9.5 cm. The vast majority of patients had undifferentiated histology (n=11, 46%) followed by liposarcoma/leiomyosarcoma (n=6, 25%), myxofibrosarcoma (n=5, 21%), and other (n=2, 8%). Tumor anatomic location was proximal lower extremity/buttock, upper extremity, distal lower extremity, and chest wall in 71%, 13%, 8%, and 8%, respectively. Most patients presented with stage III disease (79%) followed by I (13%) and II (8%). Histologic grade was high, low, and intermediate in 79%, 13%, and 8%, respectively. Two patients (8.3%) had positive margins on surgical specimens and plastic surgery was involved in 9 of the operations (38%). Median RT elapsed days was 9.5 and the median time from initiation of RT to time of surgery was 50.5 days. At a median follow-up time of 19.8 months, 6 patients (25%) experienced a post-operative wound complication. Local control was 100%. Five patients developed distant metastatic disease (20.8%) with a median time to distant metastases of 15.4 months. Two patients (8%) died of metastatic disease. Results of preoperative hypofractionated radiotherapy for treatment of patients with STS of the extremity and trunk demonstrates post-operative wound complication rates comparable to historical rates using conventionally fractionated RT. Although local control was optimal at 100%, further follow-up is needed to corroborate these findings.

Hypofractionated Radiotherapy in Locally Advanced Myxoid Liposarcomas of Extremities or Trunk Wall: Results of a Single Arm Prospective Clinical Trial

Preoperative hypofractionated radiotherapy 5x5 Gy for five consecutive days, and then immediate surgery in patients with locally advanced soft tissue sarcomas (STS) showed a good local control rate and treatment tolerance. Myxoid liposarcoma (MLPS) is highly radiosensitive as compared with other STS, thus a longer gap between the end of RT and surgery may increase the local efficacy and allow to obtain better pathological response rate. The main objective of the study was to assess the safety of 5x5 Gy hypofractionated preoperative RT with prolonged gap (6-8 weeks) to surgery in patients with locally advanced primary MLPS. In this single-arm prospective clinical trial. Patients with locally advanced MLPS underwent preoperative 5x5 Gy RT with 6-8 weeks gap between RT end and surgery from April 2015 to January 2019. The primary endpoint of the study was the rate of perioperative wound healing complications. The secondary endpoints were the pathological response according to the European Organization for Research and Treatment of Cancer - Soft Tissue and Bone Sarcoma Group recommendations (EORTC-STSBG) and local control rate at 5 years. From April 2015 until February 2019 29 patients with primary MLPS finished the whole planned protocol treatment. All of the patients had the tumors located in the lower limb. The median tumor size was 16 cm. The median follow-up time was 13 months. Perioperative wound complications occurred in 9 patients (31%). 6 patients (21%) required medical intervention (antibiotics or wound revision, grade 2 or higher according to Common Terminology Criteria for Adverse Events version 4.03). These results are similar (32.4%) to our historical controls of 272 patients with advanced STS who were treated with 5x5 Gy RT and immediate surgery. R0 margins were achieved in all but two patients (7%) who had R1 resection margin. None of the patients had local recurrence and four patients (14%) developed distant metastases at the moment of analysis (February 2019). The pathological response category according to the EORTC-STSBG recommendations were B (3.5%), C (20.7%), D (34.5%) and E (41.38%). Preoperative hypofractionated RT with the prolonged gap between the RT and surgery is a reasonable approach to MLPS treatment providing a low rate of perioperative complications and good local control.

Preoperative Hypofractionated Radiation Therapy in Soft Tissue Sarcoma of the Extremity: Outcomes from the National Cancer Database

Preoperative Hypofractionated Radiation Therapy in Soft Tissue Sarcoma of the Extremity: Outcomes from the National Cancer Database

1628P - Preoperative hypofractionated radiotherapy (RT) combined with chemotherapy in primary marginally resectable high grade soft tissue sarcomas (STS) of extremities or trunk wall: Interim analysis of prospective phase II clinical trial

Background: The management of marginally resectable STS is challenging. The study aim is to assess the efficacy and safety of preoperative hypofractionated RT combined with chemotherapy in primary locally advanced STS. Methods: Single-arm clinical trial enrolls patients for one cycle of doxorubicin and ifosfamide (AI) chemotherapy followed by 5x5 Gy RT, and 2 cycles of AI in 7-8 weeks gap between RT end and surgery. Tumor response was assessed in DWI-MR imaging and pathologically by EORTC STBSG criteria. The primary endpoint is rate of limb-sparing surgeries and R0 resections. Results: 24 patients(pts) met eligibility criteria: 21 finished the whole planned protocol treatment. 3 pts underwent extremity amputation, two after 1st AI cycle due to poor tolerance, one due to extensive tumor invasion without possibility of vessels reconstruction. One toxic death occurred outside our center related to severe bone marrow suppression with septic shock after 2nd AI cycle. Early tolerance of chemotherapy was acceptable. Grade 3+ CTCAE4.03 toxicity developed in 11pts. AI dose was reduced in 8pts who completed therapy (4pts in 2 cycles; 4pts in 1 cycle). Early RT tolerance was satisfactory. EORTC grade 1 radiation dermatitis developed in 13pts and grade 2 in 2pts. Postoperative wound complications occurred in 6pts, including 2 severe wound dehiscence with hospitalization. Very good pathological response (<1% of stainable tumor cells; grade A/B) was reported in 5pts, good pathological response (<50% tumor cells; grade C/D) - in 12pts. Conclusions: Preoperative AI chemotherapy combined with hypofractionated RT is a feasible method of the management of marginally resectable STS providing a good pathological responses and acceptable treatment toxicity. Legal entity responsible for the study: Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland. Funding: Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, Poland. Disclosure: T. Switaj: Honoraria for lectures: Novartis, Roche, MSD, BMS. A.M. Czarnecka: Honoraria for lectures: Novartis, MSD, BMS. P.L. Rutkowski: Honoraria: Bristol-Myers Squibb, Roche, Novartis, Merck, Sharp & Dohme, GlaxoSmithKline; Paid consulting role: Bristol-Myers Squibb, Roche, Merck, Sharp & Dohme, Blueprint Medicines, Amgen; Speakers’ bureau: Novartis, Pfizer, Merck, Sharp & Dohme; Institutional research funding: Bristol-Myers Squibb, Novartis; Travel expenses: Novartis. All other authors have declared no conflicts of interest.

Long-Term Results of Neoadjuvant Chemotherapy and Preoperative Hypofractionated Radiation Therapy in the Management of High-Risk Extremity Sarcomas

Long-Term Results of Neoadjuvant Chemotherapy and Preoperative Hypofractionated Radiation Therapy in the Management of High-Risk Extremity Sarcomas

Efficacy of neoadjuvant hypofractionated radiotherapy in patients with locally advanced myxoid liposarcoma

BackgroundMyxoid liposarcoma (MLPS) has been reported to be more radiosensitive compared with other soft tissue sarcomas (STS). The use of preoperative hypofractionated radiotherapy 5 × 5 Gy for five consecutive days, and then immediate surgery in patients with locally advanced STS showed a good local control rate. The main objective of our work was to assess the efficacy of hypofractionated radiotherapy in preoperative setting in patients with locally advanced primary MLPS. MethodsFrom February 1999 to March 2014, 32 patients with primary MLPS were treated with preoperative hypofractionated radiotherapy for 5 consecutive days followed by immediate surgery (median dose 5 × 5 Gy). Median size of the tumor 10.5 cm. In one patient the tumor was located on the upper extremity, the other (31 patients) had their tumors located on the lower extremity. ResultsIn 90% patients histologically negative surgical margins (R0) were obtained. 34% patients had distant recurrence of the disease, local recurrence was found in 9.3% of the patients. 5-year local relapse-free survival rate was 90% and overall survival was 68%. In all analyzed surgical specimens the radiotherapy response features (hyalinization, fibrosis, paucicelularity, hemorrhages, dilatation of vessels) were detected. We have not found statistically significant differences in terms of OS and LRFS for RCC component, tumor grade, BCL2, TP53, postsurgery necrosis and tumor size. In postradiotherapy specimens significantly higher positivity of TP53 expression was detected as compared to primary biopsies. ConclusionCombined therapy with hypofractionated radiotherapy followed by immediate surgery seems to be effective therapy in MLPS demonstrating good local control and pathological response to therapy.

Preoperative hypofractionated radiotherapy in the treatment of localized soft tissue sarcomas

BackgroundThe primary treatment of soft tissue sarcomas (STS) is a radical resection of the tumor with adjuvant radiotherapy. Conventional fractionation of preoperative radiotherapy is 50 Gy in fraction of 2 Gy a day. The purpose of the conducted study was to assess the efficacy and safety of hypofractionated radiotherapy in preoperative setting in STS patients. Methods272 patients participated in this prospective study conducted from 2006 till 2011. Tumors were localized on the extremities or trunk wall. Median tumor size was 8.5 cm, 42% of the patients had tumor larger than10 cm, whereas 170 patients (64.6%) had high grade (G3) tumors. 167 patients (61.4%) had primary tumors. Patients were treated with preoperative radiotherapy for five consecutive days in 5 Gy per fraction, with an immediate surgery. Median follow up is 35 months. Results79 patients died at the time of the analysis, the 3-year overall survival was 72%. Local recurrences were observed in 19.1 % of the patients. Factors that had a significant adverse impact on local recurrence were tumor size of10 cm or more and G3 grade. 114 patients (42%) had any kind of treatment toxicity, vast majority with tumors located on lower limbs. 7% (21) of the patients required surgery for treatment of the complications. ConclusionIn this non-selected group of locally advanced STS use of hypofractionated preoperative radiotherapy was associated with similar local control (81%) when compared to previously published studies. The early toxicity is tolerable, with small rate of late complications. Presented results warrant further evaluation.

Repeated Positron Emission Tomography-Computed Tomography and Perfusion-Computed Tomography Imaging in Rectal Cancer: Fluorodeoxyglucose Uptake Corresponds With Tumor Perfusion

The purpose of this study was to analyze both the intratumoral fluorodeoxyglucose (FDG) uptake and perfusion within rectal tumors before and after hypofractionated radiotherapy. Rectal cancer patients, referred for preoperative hypofractionated radiotherapy (RT), underwent FDG-positron emission tomography (PET)-computed tomography (CT) and perfusion-CT (pCT) imaging before the start of hypofractionated RT and at the day of the last RT fraction. The pCT-images were analyzed using the extended Kety model, quantifying tumor perfusion with the pharmacokinetic parameters K(trans), v(e), and v(p). The mean and maximum FDG uptake based on the standardized uptake value (SUV) and transfer constant (K(trans)) within the tumor were correlated. Also, the tumor was subdivided into eight subregions and for each subregion the mean and maximum SUVs and K(trans) values were assessed and correlated. Furthermore, the mean FDG uptake in voxels presenting with the lowest 25% of perfusion was compared with the FDG uptake in the voxels with the 25% highest perfusion. The mean and maximum K(trans) values were positively correlated with the corresponding SUVs (ρ = 0.596, p = 0.001 and ρ = 0.779, p < 0.001). Also, positive correlations were found for K(trans) values and SUVs within the subregions (mean, ρ = 0.413, p < 0.001; and max, ρ = 0.540, p < 0.001). The mean FDG uptake in the 25% highest-perfused tumor regions was significantly higher compared with the 25% lowest-perfused regions (10.6% ± 5.1%, p = 0.017). During hypofractionated radiotherapy, stable mean (p = 0.379) and maximum (p = 0.280) FDG uptake levels were found, whereas the mean (p = 0.040) and maximum (p = 0.003) K(trans) values were found to significantly increase. Highly perfused rectal tumors presented with higher FDG-uptake levels compared with relatively low perfused tumors. Also, intratumor regions with a high FDG uptake demonstrated with higher levels of perfusion than regions with a relatively low FDG-uptake. Early after hypofractionated RT, stable FDG uptake levels were found, whereas tumor perfusion was found to significantly increase.

Preoperative short-course radiotherapy versus combined radiochemotherapy in locally advanced rectal cancer: a multi-centre prospectively randomised study of the Berlin Cancer Society

BackgroundThe additional use of radiotherapy has changed the treatment of locally advanced rectal cancer (LARC) dramatically. But a major achievement has been the development of total mesorectal excision (TME) as a surgical standard and the recognition that the surgeon is the predominant prognostic factor. The benefit of preoperative hypofractionated radiotherapy (SCRT; five fractions each of 5 Gy), initially established by the Swedish Rectal Cancer Trial, has been demonstrated in conjunction with TME by the Dutch Colorectal Cancer Group. The concept of combined neoadjuvant radiochemotherapy (conventional radiation of about 50 Gy with chemotherapy) has not been compared over surgery alone with TME. However, the German Rectal Cancer Study Group recently demonstrated that preoperative radiochemotherapy (RCT) was better than postoperative radiochemotherapy in terms of local control.Methods and designPatients with histological proven rectal cancer staged T2N+ or T3 are randomized to receive either SCRT (25 Gy in five fractions of 5 Gy) plus TME-surgery within 5 days or RCT (50.4 Gy in 28 fractions of 1.8 Gy, continuous infusion 5-fluorouracil) plus TME-surgery 4–6 weeks later. All patients receive adjuvant chemotherapy (12 weeks continuous infusional 5-FU) and are followed up for 5 years. TME-quality is independently documented by the surgeon and the pathologist. Hypothesis of the study is that RCT is superior to SCRT in terms of local recurrence after five years. Secondary endpoints are overall survival, disease-free survival, complete resection rate (R0 resection), rate of sphincter saving resection, acute and late toxicity (radiation related side effects), and quality of life (including long term bowel function).DiscussionSimilar long-term survival, local control and late morbidity have been reported for both concepts of preoperative therapy in non-comparative studies. In addition to other ongoing (and recently published) comparative trials we include a larger number of patients for adequate power, apply quality-controlled TME and try to avoid the adjuvant treatment bias by mandatory adjuvant chemotherapy in both groups. Further more, stratification of the initially planned surgical procedure and sphincter-preservation will generate valid evidence whether RCT will allow a less aggressive (sphincter saving) surgical approach.