Intermediate-risk endometrial cancer treated with adjuvant brachytherapy using single dosimetric planning: long-term outcome and toxicity assessment.

OBJECTIVE: Brachytherapy of the vaginal dome is the recommended adjuvant treatment for intermediate-risk endometrial cancer. This study assessed the results of dosimetric planning of high-dose-rate brachytherapy exclusively in the first treatment session. STUDY DESIGN: This retrospective study included all patients who underwent hysterectomy for endometrial cancer followed by adjuvant brachytherapy of the vaginal dome between 2012 and 2015. Local recurrence rates, overall survival (OS) rates, recurrence-free survival (RFS) rates, and related acute and late toxicity rates were evaluated. RESULTS: This analysis included 250 patients, of whom 208 were considered to be at high-intermediate risk of disease recurrence. After a median follow-up of 56 months, the cumulative incidence of local recurrence was 4.8% at 3 years [95% confidence interval (CI) 2.8-8.3] and 7.8% at 5 years (95% CI 4.8-12.6). The 5-year OS rate was 86.2% (95% CI 80.6-90.3), and the 5-year RFS rate was 77.5% (95% CI 71.1-82.7). Acute toxicity occurred in 20 (8%) patients, of which two patients had grade ≥3 toxicity. Only one patient (0.4%) presented with late grade ≥3 toxicity. CONCLUSION: These findings confirm the tolerability of this brachytherapy approach, indicating minimal cases of late grade ≥3 toxicity, associated with a good 5-year OS rate. With the advent of molecular prognostic factors, the current focus revolves around discerning those individuals who gain the greatest benefit from adjuvant therapy, and tailoring treatment more effectively.

Technical Refinements and Outcomes Assessment in Prepectoral Pocket Conversion After Postmastectomy Radiotherapy.

BACKGROUND: Several studies show how submuscular breast reconstruction is linked to animation deformity, shoulder dysfunction, and increased postoperative chest pain, when compared to prepectoral breast reconstruction. In solving all these life-impairing side effects, prepectoral implant pocket conversion has shown encouraging results. OBJECTIVES: The aim of this study was to propose a refinement of the prepectoral implant pocket conversion applied to previously irradiated patients. METHODS: We conducted a retrospective study on 42 patients who underwent previous nipple- or skin-sparing mastectomy and immediate submuscular reconstruction, followed by radiotherapy. We performed fat grafting sessions as regenerative pretreatment. Six months after the last fat graft, we performed the conversion, with prepectoral placement of micropolyurethane foam-coated implants. We investigated the preconversion and postconversion differences in upper limb range of motion, Upper Extremity Functional Index, and patient satisfaction with the breast and physical well-being of the chest. RESULTS: We reported a resolution of animation deformity in 100% of cases. The range of motion and the Upper Extremity Functional Index scores were statistically improved after prepectoral implant pocket conversion. BREAST-Q scores for satisfaction with the breast and physical well-being of the chest were also improved. CONCLUSIONS: The refined prepectoral implant pocket conversion is a reliable technique for solving animation deformity and improving quality of life in patients previously treated with submuscular reconstruction and radiotherapy.

[Predictive factors assessment of pathological response to neoadjuvant radiotherapy of soft tissue sarcomas]. / Évaluation de facteurs prédictifs de réponse pathologique à la radiothérapie néoadjuvante des sarcomes des tissus mous.

PURPOSE: Conserving surgery combined with radiotherapy in presence of local recurrence risk factors is standard treatment of soft tissue sarcomas, a group of rare and heterogeneous tumours. Radiotherapy is performed before or after surgery. In neoadjuvant setting, late radiation-induced toxicity is reduced and pathological response to radiotherapy could be achieved. A complete pathological response to radiotherapy has recently been shown to predict better survival. Our study aims at identifying predictive factors of pathological response to neoadjuvant radiotherapy (clinical, radiological or histological) of soft tissue sarcomas. PATIENTS AND METHODS: Clinical, imaging (MRI: perilesional oedema, necrosis, tumour heterogeneity, vasculonervous relationships) and pathological (pathological subtype, tumour grade, anticipated/obtained resection quality) data were retrospectively collected. Tumour response (imaging and pathological), patient outcome, acute and late radiation-induced toxicity, predictive factors of pathological response to neoadjuvant radiotherapy were studied. The 2-test or exact-Fisher test (qualitative variables) and by Student's t-test or Kruskal-Wallis test (quantitative variables) were used for statistical analysis. RESULTS: From April 2017 to April 2021, neoadjuvant radiotherapy (50Gy in 25 fractions) followed by surgical excision was performed to 36 consecutive patients with liposarcomas (n=17/36), or undifferentiated sarcomas (n=8/36). MRI response was complete in 1 patient, partial in 9 patients (n=9/36, 25%), stable in 21 patients (n=21/36, 58%) or in progression in 5 patients (n=5/36, 14%). Pathological response was observed in 22 patients (61%). No grade 3-4 acute radiation-induced toxicity was observed. Regarding late toxicity, 28% of patients had grade 1-2 oedema (n=10/36), 39% had a grade 1 fibrosis (n=14/36), and 30% grade 1 pain (n=11/36). No predictive factors of response to radiotherapy was statistically significant. CONCLUSIONS: Neoadjuvant radiotherapy is well-tolerated. No clinical, radiological or pathological predictive factors was identified for radiotherapy tumour response.

Delayed-immediate breast reconstruction: An assessment of complications and outcomes in the context of anticipated post-mastectomy radiotherapy.

INTRODUCTION: The detrimental effects of post-mastectomy radiotherapy on breast reconstruction are well known. We report our experience with a delayed-immediate approach involving an initial subcutaneous implant with definitive reconstruction after adjuvant radiotherapy. METHODS: Patients were identified retrospectively from hospital, theatre and implant registry records. Details regarding demographics, cancer pathology, surgical data and oncological therapies were collected. Primary outcomes included complication rates of first-stage surgery and time to definitive reconstruction. RESULTS: A total of 115 patients underwent mastectomy and temporary subcutaneous implant (36 nipple sparing) between 2008 and 2019. Five were smokers with eleven having a body mass index > 30. The median age was 46 years (27-76 years) and tumour size 50 mm. Almost 95% underwent radiotherapy, 82% chemotherapy and 70% had axillary node clearance. Median mastectomy weight was 464 g (123-1300 g) with median temporary implant volume 375 cc (180-655 cc). Complications of first-stage surgery at three months included 5.2% implant loss (n = 6), 14.8% infection rate, 17.4% readmission rate and 10.4% returned to theatre. Reconstructive failure occurred in four cases (3.5%). A total of 76 patients completed definitive reconstruction, including 26 autologous, 21 latissimus dorsi with implant, and 28 implant-only reconstructions. The median time to reconstruction following the completion of radiotherapy was 12 months. This increased in those who had implant complications (28 vs. 15 months) or radiotherapy (16 vs. 10 months) versus those without. CONCLUSIONS: Delayed-immediate breast reconstruction using a temporary subcutaneous implant has been shown to be a safe, feasible and potentially beneficial method than simple mastectomy and delayed reconstruction with a complication rate comparable to that of immediate implant reconstruction.

The role of nutritional assessment for predicting radiotherapy-induced adverse events in patients with gastric cancer.

OBJECTIVE: The aim of this study was to investigate the role of nutritional factors in predicting radiotherapy-associated toxicities for gastric cancer patients. METHODS: A total of 285 gastric cancer patients who underwent radiotherapy in our hospital (Fudan University Shanghai Cancer Center) between 2010 and 2017 were included in this retrospective study. Nutritional status assessment included body weight loss (BWL), body mass index (BMI), serum albumin, nutrition risk screening 2002(NRS-2002), patient-generated subjective global assessment(PG-SGA) and nutritional risk index (NRI). RESULTS: Of all patients, 19.6% were underweight (BMI<18.5 kg/m2), 25.6% were hypoalbuminemia (<35 g l-1) and 48.8% lost ≥10% of body weight in the 6-month interval before radiotherapy(BWL). Meanwhile, 73.3%, 78.6 and 47.2% of the patients were diagnosed as malnutrition based on NRS-2002, PG-SGA and NRI, respectively. Hematological adverse events were present in 91.2% (≥Grade 1) and 20.4% (≥Grade 3) of the patients. Non-hematological adverse events occurred in 89.8% (≥Grade1) and 14.4% (≥Grade 3) of the patients. Multivariate analyses indicated that only hypoalbuminemia(<35 g l-1) was independent predictor for Grade 3/4 hematological and non-hematological adverse events. Meanwhile, higher BWL(≥10%) was also independent predictor for Grade 3/4 non-hematological adverse events. NRS-2002, PG-SGA and NRI score were not associated with treatment-induced adverse events. CONCLUSION: BWL and serum albumin are useful factors for predicting severe adverse events in gastric cancer patients who undergo radiotherapy. ADVANCES IN KNOWLEDGE: The use of nutritional factors in predicting severe adverse events enables implementation of individualized treatment strategies for early and intensive nutritional interventions in high-risk patients.

Risk factors for lymphedema and method of assessment in endometrial cancer: a prospective longitudinal multicenter study.

OBJECTIVE: The aim of the study was to determine risk factors for lymphedema of the lower limbs, assessed by four methods, 1 year after surgery for endometrial cancer. METHODS: A prospective longitudinal multicenter study was conducted in 14 Swedish hospitals. 235 women with endometrial cancer were included; 116 underwent surgery including lymphadenectomy, and 119 had surgery without lymphadenectomy. Lymphedema was assessed preoperatively and 1 year postoperatively objectively by systematic circumferential measurements of the legs, enabling volume estimation addressed as (1) crude volume and (2) body mass index-standardized volume, or (3) clinical grading, and (4) subjectively by patient-reported perception of leg swelling. In volume estimation, lymphedema was defined as a volume increase ≥10%. Risk factors were analyzed using forward stepwise logistic regression models and presented as adjusted odds ratio (aOR) and 95% confidence interval (95% CI). RESULTS: Risk factors varied substantially, depending on the method of determining lymphedema. Lymphadenectomy was a risk factor for lymphedema when assessed by body mass index-standardized volume (aOR 14.42, 95% CI 3.49 to 59.62), clinical grading (aOR 2.11, 95% CI 1.04 to 4.29), and patient-perceived swelling (aOR 2.51, 95% CI 1.33 to 4.73), but not when evaluated by crude volume. Adjuvant radiotherapy was only a risk factor for lymphedema when assessed by body mass index-standardized volume (aOR 15.02, 95% CI 2.34 to 96.57). Aging was a risk factor for lymphedema when assessed by body mass index-standardized volume (aOR 1.07, 95% CI 1.00 to 1.15) and patient-perceived swelling (aOR 1.06, 95% CI 1.02 to 1.10), but not when assessed by crude volume or clinical grading. Increase in body mass index was a risk factor for lymphedema when estimated by crude volume (aOR 1.92, 95% CI 1.36 to 2.71) and patient-perceived swelling (aOR 1.36, 95% CI 1.11 to 1.66), but not by body mass index-standardized volume or clinical grading. The extent of lymphadenectomy was strongly predictive for the development of lymphedema when assessed by body mass index-standardized volume and patient-perceived swelling, but not by crude volume or clinical grading. CONCLUSION: Apparent risk factors for lymphedema differed considerably depending on the method used to determine lymphedema. This highlights the need for a 'gold standard' method when addressing lymphedema for determining risk factors.

[Concurrent radiation therapy and dual HER2 blockade in breast cancer: Assessment of toxicity]. / Association du double blocage de HER2 et radiothérapie dans la prise en charge du cancer du sein exprimant HER2.

PURPOSE: The tolerance of the concurrent use of radiotherapy, pertuzumab and trastuzumab is unknown. The purpose of this study was to evaluate the toxicity of this association in patients treated for HER2 positive metastatic and/or locally recurrent unrespectable breast cancer. MATERIAL AND METHODS: A retrospective study was performed in our institution for all consecutive patients treated with concurrent irradiation, pertuzumab and trastuzumab. The radiotherapy was performed while pertuzumab and trastuzumab were administrated as a maintenance treatment at the dose of 420mg (total dose) and 6mg/kg respectively every 3 weeks without chemotherapy. Toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Left ventricular ejection fraction (LVEF) was measured at baseline and then every 3-4 months. RESULTS: We studied 77 patients. treated in between 2013 and 2019 with median follow-up of 38 months (range 0-264 months). Median age was 53 years (33-86). There were 50 patients (64.9%) with metastatic and 27 patients (35.1%) with recurrent disease. All patients received docetaxel followed by P-T as first line treatment and they received 34 cycles (10-85) of pertuzumab and trastuzumab. All patients experienced partial or complete response according to RECIST criteria. Irradiation volumes were whole breast (41 patients, 53.2%) and chest wall (29 patients, 37.7%) at a dose of 50Gy with a median duration of 39 days. Radiotherapy of lymph nodes was performed in 53 patients (68.8%) as following: supraclavicular-infraclavicular and axillary lymph nodes in 52 patients (67.5%), and internal mammary nodes in 31 patients (40.3%). For 20 patients. (26.0%) radiotherapy was palliative: bone irradiation (12 patients, 15.6%), whole-brain radiotherapy (2 patients, 2.6%), cerebral metastasis irradiation (6 patients). As early toxicity we observed: radio dermatitis as following: 36 patients (46.8%) presented grade I, 17 patients (22.1%) presented grade II, and 3 patients (3.9%) presented grade III. One patient (1.3%) presented grade II esophagitis. One patient (1.3%) presented asymptomatic decrease of LVEF during treatment and 6 patients (7.7%) presented a decrease of LVEF. There was no radiation-induced pneumonitis. As late toxicity, we observed 1 (1.3%) case of grade I and 1 (1.3%) with grade II telangiectasia. There was 1 case (1.3%) of grade III cardiac toxicity, 8 months after the concurrent treatment. CONCLUSION: The concurrent use of radiotherapy, pertuzumab and trastuzumab is feasible with good tolerance. Larger prospective data with longer follow-up is needed to confirm these results.

Costs of Definitive Chemoradiation, Surgery, and Adjuvant Radiation Versus De-Escalated Adjuvant Radiation per MC1273 in HPV+ Cancer of the Oropharynx.

PURPOSE: De-escalated treatment for human papillomavirus (HPV)+ oropharynx squamous cell carcinoma (OPSCC) has shown promising initial results. Health-care policy is increasingly focusing on high-value care. This analysis compares the cost of care for HPV+ OPSCC treated with definitive chemoradiation (CRT), surgery and adjuvant radiation (RT), and surgery and de-escalated CRT on MC1273. METHODS AND MATERIALS: MC1273 is a prospective, phase 2 study evaluating adjuvant CRT to 30 to 36 Gy plus docetaxel for HPV+ OPSCC after surgery for high-risk patients. Matched standard-of-care control groups were retrospectively identified for patients treated with definitive CRT or adjuvant RT. Standardized costs were evaluated before radiation, during treatment (during RT), and at short-term (6 month) and long-term (7-24 month) follow-up periods. RESULTS: A total of 56 definitive CRT, 101 adjuvant RT, and 66 MC1273 patients were included. The CRT arm had more T3-4 disease (63% vs 17-21%) and higher N2c-N3 disease (52% vs 20-24%) vs both other groups. The total treatment costs in the CRT, adjuvant RT, and MC1273 groups were $47,763 (standard deviation [SD], $19,060], $57,845 (SD, $17,480), and $46,007 (SD, $9019), respectively, and the chemotherapy and/or RT costs were $39,936 (SD, $18,480), $26,603 (SD, $12,542), and $17,864 (SD, $3288), respectively. The per-patient, per-month, average short-term follow-up costs were $3860 (SD, $10,525), $1072 (SD, $996), and $972 (SD, $833), respectively, and the long-term costs were $978 (SD, $2294), $485 (SD, $1156), and $653 (SD, $1107), respectively. After adjustment for age, T-stage, and N-stage, treatment costs remained lower for CRT and MC1273 versus adjuvant RT ($45,450 and $47,114 vs $58,590, respectively; P < .001), whereas the total per-patient, per-month follow-up costs were lower in the MC1273 study group and adjuvant RT versus CRT ($853 and $866 vs $2030, respectively; P = .03). CONCLUSIONS: MC1273 resulted in 10% and 20% reductions in global costs compared with standard-of-care adjuvant RT and definitive CRT treatments. Substantial cost savings may be an added benefit to the already noted low toxicity and maintained quality of life of treatment per MC1273.

Shoulder function after neck dissection: Assessment via a shoulder-specific quality-of-life questionnaire and active shoulder abduction.

OBJECTIVE: Neck dissection results in a high probability of postoperative shoulder functional impairment, even when the spinal accessory nerve is preserved. Therefore, surgeons must inform patients about the expected functional and qualitative recovery of shoulder function after surgery. METHODS: The present study included a prospective cohort of 66 patients (85 neck dissection sides) who underwent neck dissection between December 2015 and July 2017 at a single institution. The active shoulder abduction angles of the affected side and the patient-reported shoulder-specific quality-of-life recovery score of the Western Ontario Rotator Cuff (WORC) questionnaire were examined at 1, 3, 6, 9, and 12 months postoperatively. Additionally, the association between these outcomes and risk factors for shoulder impairment were investigated. RESULTS: The average active shoulder abduction angles were significantly improved at 3 and 6 months postoperatively compared with 1 month postoperatively (96.5 ± 4.3° at 1 month versus 110.1 ± 4.7° at 3 months, p = 0.035, and versus 142.0 ± 4.6° at 6 months, p < 0.0001). The proportion of patients who were unable to abduct their shoulders by 150° or more was significantly lower at 6 months postoperatively (41.5%) compared with 1 month postoperatively (82.4%, p < 0.0001). The WORC score significantly improved from 60.4 ± 2.4% at 1 month postoperatively to 67.9 ± 2.6% at 6 months postoperatively (p = 0.036). Multivariate analysis revealed that postoperative radiotherapy was a significant risk factor for shoulder impairment at 3 and 6 months postoperatively (p = 0.003 and p = 0.027, respectively), and that level V dissection and head and neck irradiation were significant risk factors for a worse shoulder outcome at 6 and 9 months postoperatively (respective p values for level V dissection and head and neck irradiation were p = 0.049 and p = 0.030 at 6 months postoperatively, and p = 0.016 and p = 0.013 at 9 months postoperatively). CONCLUSION: Satisfactory functional and qualitative recovery of shoulder function was achieved at 6 months after neck dissection. Postoperative radiotherapy was a predictor of poor shoulder function in the early postoperative period; both level V dissection and head and neck irradiation were predictors of poor shoulder function at 6 and 9 months after neck dissection.

The Use of Absorbable Mesh in Implant-Based Breast Reconstruction: A 7-Year Review.

BACKGROUND: Breast reconstruction is most frequently performed using implants or expanders. Adjunctive materials such as acellular dermal matrix and synthetic meshes are used to support the implant or expander. A paucity of large studies exist on the use of synthetic mesh for breast reconstruction. METHODS: A retrospective chart review of all patients over the past 7 years who had implant reconstruction with synthetic absorbable mesh at the Massachusetts General Hospital was performed. Data were collected on demographic and surgical outcomes. Statistical analysis was performed. RESULTS: A total of 227 patients (376 mastectomies) were treated with direct-to-implant subpectoral reconstruction with absorbable mesh from 2011 to 2017. The infection rate was 2.1 percent. The rate of capsular contracture was 4.8 percent. Patients who had radiation therapy either preoperatively or postoperatively had a higher rate of complications, including capsular contracture. Cost savings for using mesh instead of acellular dermal matrix surpassed $1.2 million. CONCLUSION: Synthetic absorbable mesh is a safe alternative to acellular dermal matrix in prosthetic breast reconstruction and provides stable results along with significant cost savings. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Toxicity after adjuvant therapy for stage III uterine cancer.

OBJECTIVE: The optimal adjuvant therapy for stage III endometrial cancer is unknown. Studies have suggested that combination therapy with chemotherapy and radiation is associated with improved survival. We examined early and late-term toxicities associated with chemotherapy (CT), external beam radiotherapy (RT), or combination chemoradiotherapy for stage III uterine cancer. METHODS: The SEER-Medicare database was used to identify women age ≥ 65 years with stage III uterine cancer who received adjuvant CT, RT, or chemoradiotherapy from 2000 to 2015. The associations between therapy and early and late-term toxicities identified with billing claims, hospitalizations and emergency department visits were examined using multivariable regression models. RESULTS: A total of 2185 patients were identified including 574 (26.3%) who received CT, 636 (29.1%) who received RT, and 975 (44.6%) who received chemoradiotherapy. The proportion of patients receiving chemoradiotherapy or CT increased over time. During the first 6 and 12 months of adjuvant therapy, RT was associated with a lower risk of early-term toxicity compared to chemoradiotherapy (aRR = 0.59, 95%CI 0.49-0.70 and aRR = 0.76, 95%CI 0.67-0.86, respectively) while CT shared a similar risk of early toxicities as chemoradiotherapy. CT and RT shared a similar risk of late-term toxicities compared to chemoradiotherapy. CT and RT alone were associated with a higher hazard for overall mortality than chemoradiotherapy (aHR = 1.27, 95% CI 1.10-1.47 and aHR = 1.25, 95% CI 1.08-1.44, respectively). CONCLUSION: Chemoradiotherapy is associated with lower mortality compared to single modality therapy and has a similar risk of early and late term toxicities compared to CT, though higher risk of early toxicities compared to RT.

Assessment of toxicities and outcomes in patients with breast cancer treated with hypofractionated radiotherapy.

BACKGROUND: Hypofractionation is now becoming the standard of care in breast irradiation. The aim of this study was to assess the toxicities and outcomes in patients with breast cancer treated with hypofractionated radiotherapy (HFRT). METHODS: Patients with localized breast cancer who received adjuvant HFRT between 2013 and 2015 with a minimum follow-up of 6 months following radiation were included in this prospective study. Late toxicities were assessed using CTCAE v 4 and included chest/breast pain, limb pain, limb edema, skin pigmentation, skin fibrosis, and shoulder movement restriction. Outcomes assessed included locoregional control, disease-free survival, and overall survival. Statistical analysis was done using Microsoft Excel and SPSS v22. RESULTS: A total of 81 patients fulfilled the inclusion criteria, of which 19 patients had died during follow-up. Regional nodal irradiation was done in 63 (77.8%) patients using the same hypofractionated schedule of 40 Gy in 15 fractions. Late toxicities were assessed for 62 patients. The median follow-up following the course of hypofractionated radiation was 45 months (range 14 - 65 months). Late toxicities were assessed for 62 patients. Grade 1/2 chest/breast pain, limb pain, limb edema, skin pigmentation, skin fibrosis, and shoulder movement restriction were seen in 11%, 12%, 7%, 6%, 8%, and 11% of cases, respectively. Distant recurrences were seen in 8% of cases, and there were no locoregional recurrences. Five-year overall survival was 76.5%. CONCLUSION: HFRT to whole breast or chest wall and the regional nodal areas was well-tolerated with acceptable rates of late toxicities on follow-up.

Design of the PROstate cancer follow-up care in Secondary and Primary hEalth Care study (PROSPEC): a randomized controlled trial to evaluate the effectiveness of primary care-based follow-up of localized prostate cancer survivors.

BACKGROUND: In its 2006 report, From cancer patient to cancer survivor: lost in transition, the U.S. Institute of Medicine raised the need for a more coordinated and comprehensive care model for cancer survivors. Given the ever increasing number of cancer survivors, in general, and prostate cancer survivors, in particular, there is a need for a more sustainable model of follow-up care. Currently, patients who have completed primary treatment for localized prostate cancer are often included in a specialist-based follow-up care program. General practitioners already play a key role in providing continuous and comprehensive health care. Studies in breast and colorectal cancer suggest that general practitioners could also consider to provide survivorship care in prostate cancer. However, empirical data are needed to determine whether follow-up care of localized prostate cancer survivors by the general practitioner is a feasible alternative. METHODS: This multicenter, randomized, non-inferiority study will compare specialist-based (usual care) versus general practitioner-based (intervention) follow-up care of prostate cancer survivors who have completed primary treatment (prostatectomy or radiotherapy) for localized prostate cancer. Patients are being recruited from hospitals in the Netherlands, and randomly (1:1) allocated to specialist-based (N = 195) or general practitioner-based (N = 195) follow-up care. This trial will evaluate the effectiveness of primary care-based follow-up, in comparison to usual care, in terms of adherence to the prostate cancer surveillance guideline for the timing and frequency of prostate-specific antigen assessments, the time from a biochemical recurrence to retreatment decision-making, the management of treatment-related side effects, health-related quality of life, prostate cancer-related anxiety, continuity of care, and cost-effectiveness. The outcome measures will be assessed at randomization (≤6 months after treatment), and 12, 18, and 24 months after treatment. DISCUSSION: This multicenter, prospective, randomized study will provide empirical evidence regarding the (cost-) effectiveness of specialist-based follow-up care compared to general practitioner-based follow-up care for localized prostate cancer survivors. TRIAL REGISTRATION: Netherlands Trial Registry, Trial NL7068 (NTR7266). Prospectively registered on 11 June 2018.

Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial.

BACKGROUND: We aimed to identify a five-fraction schedule of adjuvant radiotherapy (radiation therapy) delivered in 1 week that is non-inferior in terms of local cancer control and is as safe as an international standard 15-fraction regimen after primary surgery for early breast cancer. Here, we present 5-year results of the FAST-Forward trial. METHODS: FAST-Forward is a multicentre, phase 3, randomised, non-inferiority trial done at 97 hospitals (47 radiotherapy centres and 50 referring hospitals) in the UK. Patients aged at least 18 years with invasive carcinoma of the breast (pT1-3, pN0-1, M0) after breast conservation surgery or mastectomy were eligible. We randomly allocated patients to either 40 Gy in 15 fractions (over 3 weeks), 27 Gy in five fractions (over 1 week), or 26 Gy in five fractions (over 1 week) to the whole breast or chest wall. Allocation was not masked because of the nature of the intervention. The primary endpoint was ipsilateral breast tumour relapse; assuming a 2% 5-year incidence for 40 Gy, non-inferiority was predefined as ≤1·6% excess for five-fraction schedules (critical hazard ratio [HR] of 1·81). Normal tissue effects were assessed by clinicians, patients, and from photographs. This trial is registered at isrctn.com, ISRCTN19906132. FINDINGS: Between Nov 24, 2011, and June 19, 2014, we recruited and obtained consent from 4096 patients from 97 UK centres, of whom 1361 were assigned to the 40 Gy schedule, 1367 to the 27 Gy schedule, and 1368 to the 26 Gy schedule. At a median follow-up of 71·5 months (IQR 71·3 to 71·7), the primary endpoint event occurred in 79 patients (31 in the 40 Gy group, 27 in the 27 Gy group, and 21 in the 26 Gy group); HRs versus 40 Gy in 15 fractions were 0·86 (95% CI 0·51 to 1·44) for 27 Gy in five fractions and 0·67 (0·38 to 1·16) for 26 Gy in five fractions. 5-year incidence of ipsilateral breast tumour relapse after 40 Gy was 2·1% (1·4 to 3·1); estimated absolute differences versus 40 Gy in 15 fractions were -0·3% (-1·0 to 0·9) for 27 Gy in five fractions (probability of incorrectly accepting an inferior five-fraction schedule: p=0·0022 vs 40 Gy in 15 fractions) and -0·7% (-1·3 to 0·3) for 26 Gy in five fractions (p=0·00019 vs 40 Gy in 15 fractions). At 5 years, any moderate or marked clinician-assessed normal tissue effects in the breast or chest wall was reported for 98 of 986 (9·9%) 40 Gy patients, 155 (15·4%) of 1005 27 Gy patients, and 121 of 1020 (11·9%) 26 Gy patients. Across all clinician assessments from 1-5 years, odds ratios versus 40 Gy in 15 fractions were 1·55 (95% CI 1·32 to 1·83, p<0·0001) for 27 Gy in five fractions and 1·12 (0·94 to 1·34, p=0·20) for 26 Gy in five fractions. Patient and photographic assessments showed higher normal tissue effect risk for 27 Gy versus 40 Gy but not for 26 Gy versus 40 Gy. INTERPRETATION: 26 Gy in five fractions over 1 week is non-inferior to the standard of 40 Gy in 15 fractions over 3 weeks for local tumour control, and is as safe in terms of normal tissue effects up to 5 years for patients prescribed adjuvant local radiotherapy after primary surgery for early-stage breast cancer. FUNDING: National Institute for Health Research Health Technology Assessment Programme.

Efficacy and toxicity of particle radiotherapy in WHO grade II and grade III meningiomas: a systematic review.

OBJECTIVEAdjuvant radiotherapy has become a common addition to the management of high-grade meningiomas, as immediate treatment with radiation following resection has been associated with significantly improved outcomes. Recent investigations into particle therapy have expanded into the management of high-risk meningiomas. Here, the authors systematically review studies on the efficacy and utility of particle-based radiotherapy in the management of high-grade meningioma.METHODSA literature search was developed by first defining the population, intervention, comparison, outcomes, and study design (PICOS). A search strategy was designed for each of three electronic databases: PubMed, Embase, and Scopus. Data extraction was conducted in accordance with the PRISMA guidelines. Outcomes of interest included local disease control, overall survival, and toxicity, which were compared with historical data on photon-based therapies.RESULTSEleven retrospective studies including 240 patients with atypical (WHO grade II) and anaplastic (WHO grade III) meningioma undergoing particle radiation therapy were identified. Five of the 11 studies included in this systematic review focused specifically on WHO grade II and III meningiomas; the others also included WHO grade I meningioma. Across all of the studies, the median follow-up ranged from 6 to 145 months. Local control rates for high-grade meningiomas ranged from 46.7% to 86% by the last follow-up or at 5 years. Overall survival rates ranged from 0% to 100% with better prognoses for atypical than for malignant meningiomas. Radiation necrosis was the most common adverse effect of treatment, occurring in 3.9% of specified cases.CONCLUSIONSDespite the lack of randomized prospective trials, this review of existing retrospective studies suggests that particle therapy, whether an adjuvant or a stand-alone treatment, confers survival benefit with a relatively low risk for severe treatment-derived toxicity compared to standard photon-based therapy. However, additional controlled studies are needed.

Comparison  of  efficacy, safety, and costs between neoadjuvant hypofractionated radiotherapy and conventionally fractionated radiotherapy for esophageal carcinoma.

BACKGROUND: We compared the efficacy, safety, and costs of hypofractionated radiotherapy (HFRT) and conventional fractionated radiotherapy (CFRT) for the neoadjuvant treatment of esophageal cancer. MATERIALS AND METHODS: Overall, 110 patients with esophageal cancer treated with neoadjuvant chemoradiotherapy from October 2002 to July 2017 were retrospectively included and divided into a HFRT group (42 patients received 30 Gray [Gy]/10 fractions for 2 weeks) and a CFRT group [68 patients received 40 Gy/20 fractions for 4 weeks]. Concurrent chemotherapy comprised cisplatin combined with either 5-FU or taxane. Surgery was performed 3-8 weeks after radiotherapy. We compared the outcomes, adverse events, and costs between the two groups. RESULTS: Pathological downstaging was achieved in 78.6% of the HFRT group and 83.8% of the CFRT group (P = 0.612). Compared with the CFRT group, the HFRT group had similar pathological complete response (pCR) (33.3% vs 35.3%; P = 0.834), median overall survival (OS) (40.8 months vs 44.9 months; P = 0.772) and progression free survival (32.7 months vs 35.4 months; P = 0.785). The perioperative complication rates were also similar between the groups, but the treatment time and costs were significantly reduced in the HFRT group (P < 0.05). Finally, multivariate analysis identified cN0 stage, pathological downstaging and pCR as independent predictors of better OS. CONCLUSION: Preoperative HFRT is effective and safe for esophageal cancer. Moreover, it is similar to CFRT in terms of overall survival and toxicity and is cost effective and less time consuming.

Adjuvant radiotherapy for uterine carcinosarcoma: A retrospective assessment of treatment outcomes.

OBJECTIVES: The objective of the study is to understand the impact of adjuvant radiotherapy (RT) and prognostic factors for patients diagnosed with uterine carcinosarcoma. MATERIALS AND METHODS: The records of 31 patients receiving adjuvant RT between the dates of September 2003-January 2013 in our clinic were evaluated retrospectively. Surgery was performed in 27 (87%) patients as staging laparotomy, for 4 patients as total abdominal hysterectomy and bilateral salpingo-oophorectomy. Pelvic external beam radiotherapy (EBRT) was 4500-5040 cGy in 25-28 fractions. In addition, 23 patients received brachytherapy following EBRT, 12 patients received adjuvant, and 1 patient received neoadjuvant chemotherapy (CT). RESULTS: The median age was 63 (between 30 and 78). The stage distribution of the patients was as follows: Stage I, 20 (64%); Stage II, 7 (23%), and Stage III, 4 (13%) patients. Five-year locoregional control (LRC) rate was 100%, disease-free survival (DFS) and overall survival (OS) rates were 65.5% and 66.2%, respectively. Stage I or II patients have a tendency for better 5-year OS and DFS rates than Stage III patients (73.1% vs. 42.9% and 72.7% vs. 42.9%; P = 0.065 and 0.051). Regarding lymph node dissection was performed or not, 5-year OS (64.7% vs. 75.0%) was not statistically different between groups (P = 0.77). Five-year OS and DFS rates were 69.2% and 61.5% for patients receiving CT (adjuvant or neoadjuvant) versus 63.7% and 68.8% for patients not receiving CT; P = 0.63 and P = 0.89, respectively. Based on the analysis of peritoneal washings, 5-year OS was 0% for patients with malignant or suspicious cytology whereas 89% for patients with benign cytology (P = 0.000). A negative correlation was observed between mitotic count of sarcomatous component and DFS time (rs = -0.812 and P = 0.05). CONCLUSIONS: Surgery and adjuvant RT seem beneficial for excellent LRC rate. However, survival rates are low due to distant metastases. Thus, there is a great need for better systemic therapies.

Survivors' perspectives on risks and benefits of Hodgkin lymphoma treatment: results of a survey by the German Hodgkin Study Group.

We performed a survey in Hodgkin lymphoma survivors to learn more about their perspectives on treatment risks and benefits. We sent questions to 1149 survivors from the GHSG's HD13-15 trials with (N = 249) or without (N =900) documented progression or relapse. The participation rate was 52% (N =581). After median follow-up of 106 months, 40% of relapse-free and over 60% of relapsed survivors were still worried about late effects and the possibility of relapse. Chemotherapy, largely independent of its intensity, had been a strain on 74% of relapse-free and 90% of relapsed survivors. Most physical, psychological, and socio-economic sequelae were more frequent among relapsed survivors (p < .05) and described as very burdensome. 74% of relapse-free and 61% of relapsed survivors considered primary cure from Hodgkin lymphoma as the most important aspect in the choice of treatment. Accordingly, primary optimal lymphoma control is of utmost importance from the patients' perspective.

Comparison of radiation dermatitis between hypofractionated and conventionally fractionated postoperative radiotherapy: objective, longitudinal assessment of skin color.

This study aimed to quantitatively compare radiation dermatitis due to hypofractionated (Hypo) and conventionally fractionated (Conv) external-beam radiotherapy in patients who underwent postoperative radiotherapy after breast-conserving surgery. Skin color changes, in terms of L* (brightness, white-black), a* (red-green), and b* (yellow-blue) values, due to external-beam radiotherapy were examined at alternate fractions using an objective method. Twenty-six patients were included in the Hypo group (42.56 Gy/16 fractions) and 46 in the Conv group (50 Gy/25 fractions). Radiotherapy decreased the L* value (darker) and increased the a* value (redder) gradually. These color alterations progressed linearly according to elapsed fractions and were similar between Hypo and Conv per fraction. The Hypo group showed significantly milder alterations in L* and a* values than the Conv group. The maximal dosage was significantly correlated to alterations in L* and a* values. Common Terminology Criteria for Adverse Events v4 assessment did not show a statistically significant difference between the Hypo (Grade 0:1:2 = 2:24:1) and Conv (1:39:6, p = 0.25) groups. The results of our objective analysis revealed that patients undergoing Hypo show milder color alteration than those undergoing Conv and that the maximal dosage is a useful predicator of color alteration.

A Phase 2 Study of 2 Weeks of Adjuvant Whole Breast/Chest Wall and/or Regional Nodal Radiation Therapy for Patients With Breast Cancer.

PURPOSE: To report the results in terms of feasibility and early toxicity of hypofractionated adjuvant whole breast/chest wall and/or regional nodal radiation therapy for patients with breast cancer. METHODS AND MATERIALS: From June 2013 to October 2014, 50 patients with breast cancer after mastectomy or after breast conservation surgery (BCS) were prospectively included. The institutional ethics committee approved the study, which was registered with ClinicalTrials.gov (ClinicalTrials.gov identifier no. NCT02460744). Treatment planning was performed using a simulator with 2 tangential fields to the breast/chest wall and an incident field to the supraclavicular fossa. The radiation dose delivered was 34 Gy in 10 fractions within 2 weeks, followed by a boost of 10 Gy in 5 fractions within 1 week for patients who underwent BCS. Acute skin toxicities were recorded during and after treatment according to the Radiation Therapy Oncology Group acute radiation toxicity scoring criteria. The primary objective was to obtain estimates of the acute toxicity rates and cosmetic outcomes that could be used to design a subsequent phase III comparative study. Acute skin and late toxicities were recorded during and after treatment. Cosmetic outcomes were assessed before and after treatment and during the regular follow-up period. A cost/benefit analysis was also performed and compared with that for standard treatment of 35 Gy in 15 fractions within 3 weeks. RESULTS: The median follow-up was 39 months (range 14-48). The mean age was 51 years (range 26-75). A left-sided tumor was present in 25 patients (50%). Total mastectomy with axillary clearance was performed in 40 (80%) and BCS in 10 (20%) patients. Acute grade 2 and 3 skin toxicity was seen in 16 (32%) and 1 (2%) patient, respectively. In the BCS patients, grade 2 skin and subcutaneous toxicity was seen in 2 (20%) and 1 (10%) patient, respectively. Grade 2 edema was seen in 1 patient (10%). The cosmesis was excellent or good in 8 (80%) and fair or poor in 2 (20%) patients. The cost/benefit analysis revealed significantly less financial burden on the patients with 2 weeks of treatment. Disease-free and overall survival at 3 years was 94% and 96%, respectively. CONCLUSIONS: Hypofractionated radiation therapy within 2 weeks appears to be feasible for patients with breast cancer and was associated with acute and late skin toxicity profiles similar to those observed with 3 weeks of treatment. The financial burden on the patient and family could be reduced with 2 weeks of treatment. Long-term follow-up data and a prospective comparative study are needed to strengthen these results. Hypofractionation might help radiation centers worldwide to meet the increasing need for radiation for breast cancer, especially in developing countries where resources are limited and patients must travel long distances for treatment.