Breast conserving surgery with intraoperative electron beam radiation therapy for low-risk breast cancer: Five-year follow-up of 306 patients.

Recent studies have reported a higher than expected risk of ipsilateral breast tumor recurrence (IBTR) after breast conserving surgery (BCS) and a single dose of electron beam intra-operative radiotherapy (IORT). This finding was the rationale to perform a retrospective single center cohort study evaluating the oncologic results of consecutive patients treated with BCS and IORT. Women were eligible if they had clinical low-risk (N0, ≤2 cm unifocal, Bloom and Richardson grade 1-2), estrogen receptor-positive and human-epidermal-growth-factor-receptor-2-negative breast cancer. Prior to BCS, pN0 status was determined by sentinel lymph node biopsy. Data on oncologic follow-up were analyzed. Between 2012 and 2019, 306 consecutive patients were treated and analyzed, with a median age of 67 (50-86) years at diagnosis. Median follow-up was 60 (8-120) months. Five-year cumulative risk of IBTR was 13.4% (95% confidence interval [CI] 9.4-17.4). True in field recurrence was present in 3.9% of the patients. In 4.6% of the patients, the IBRT was classified as a local recurrence due to seeding of tumor cells in the cutis or subcutis most likely related to percutaneous biopsy. In 2.9% of the patients, the IBRT was a new outfield primary tumor. Three patients had a regional lymph node recurrence and two had distant metastases as first event. One breast cancer-related death was observed. Estimated 5-year overall survival was 89.8% (95% CI 86.0-93.6). In conclusion, although some of IBTR cases could have been prevented by adaptations in biopsy techniques and patient selection, BCS followed by IORT was associated with a substantial risk of IBTR.

Narrowing the difference in dose delivery for IOERT and IOBT for locally advanced and locally recurrent rectal cancer.

Purpose: Intra-operative radiotherapy (IORT) has been used as a tool to provide a high-dose radiation boost to a limited volume of patients with fixed tumors with a likelihood of microscopically involved resection margins, in order to improve local control. Two main techniques to deliver IORT include high-dose-rate (HDR) brachytherapy, termed 'intra-operative brachytherapy' (IOBT), and electrons, termed 'intra-operative electron radiotherapy' (IOERT), both having very different dose distributions. A recent paper described an improved local recurrence-free survival favoring IOBT over IOERT for patients with locally advanced or recurrent rectal cancer and microscopically irradical resections. Although several factors may have contributed to this result, an important difference between the two techniques was the higher surface dose delivered by IOBT. This article described an adaptation of IOERT technique to achieve a comparable surface dose as dose delivered by IOBT. Material and methods: Two steps were taken to increase the surface dose for IOERT: 1. Introducing a bolus to achieve a maximum dose on the surface, and 2. Re-normalizing to allow for the same prescribed dose at reference depth. Conclusions: We describe and propose an adaptation of IOERT technique to increase surface dose, decreasing the differences between these two techniques, with the aim of further improving local control. In addition, an alternative method of dose prescription is suggested, to consider improved comparison with other techniques in the future.

Patients' and clinicians' preferences in adjuvant treatment for high-risk endometrial cancer: Implications for shared decision making.

BACKGROUND: Decision making regarding adjuvant therapy for high-risk endometrial cancer is complex. The aim of this study was to determine patients' and clinicians' minimally desired survival benefit to choose chemoradiotherapy over radiotherapy alone. Moreover, influencing factors and importance of positive and negative treatment effects (i.e. attribute) were investigated. METHODS: Patients with high-risk endometrial cancer treated with adjuvant pelvic radiotherapy with or without chemotherapy and multidisciplinary gynaecologic oncology clinicians completed a trade-off questionnaire based on PORTEC-3 trial data. RESULTS: In total, 171 patients and 63 clinicians completed the questionnaire. Median minimally desired benefit to make chemoradiotherapy worthwhile was significantly higher for patients versus clinicians (10% vs 5%, p = 0.02). Both patients and clinicians rated survival benefit most important during decision making, followed by long-term symptoms. Older patients (OR 0.92 [95%CI 0.87-0.97]; p = 0.003) with comorbidity (OR 0.34 [95% CI 0.12-0.89]; p = 0.035) had lower preference for chemoradiotherapy, while patients with better numeracy skills (OR 1.2 [95%CI 1.05-1.36], p = 0.011) and chemoradiotherapy history (OR 25.0 [95%CI 8.8-91.7]; p < 0.001) had higher preference for chemoradiotherapy. CONCLUSIONS: There is a considerable difference in minimally desired survival benefit of chemoradiotherapy in high-risk endometrial cancer among and between patients and clinicians. Overall, endometrial cancer patients needed higher benefits than clinicians before preferring chemoradiotherapy.

Dose-Dependent Effect of Platinum-Based Chemotherapy on the Risk of Metachronous Contralateral Testicular Cancer.

PURPOSE: Patients with testicular germ cell tumor (TGCT) are at increased risk of developing a contralateral TGCT (CTGCT). Although some studies suggest that prior treatment with platinum-based chemotherapy affects CTGCT risk, a relationship between CTGCT risk and platinum dose has not previously been assessed. We analyzed the association between the number of platinum-based chemotherapy cycles and CTGCT risk. PATIENTS AND METHODS: The risk of developing a metachronous CTGCT was evaluated in a nationwide cohort of 4,755 patients diagnosed with primary TGCT in the Netherlands between 1989 and 2007. Standardized incidence ratios were computed to compare CTGCT incidence with expected TGCT on the basis of TGCT incidence in the general population. The cumulative incidence of CTGCT was estimated in the presence of death as competing risk. The effect of treatment with platinum-based chemotherapy on CTGCT risk was assessed using multivariable Cox proportional hazards regression models. RESULTS: CTGCT was diagnosed in 136 patients (standardized incidence ratio, 14.6; 95% CI, 12.2 to 17.2). The cumulative incidence increased up to 20 years after primary diagnosis, reaching 3.4% (95% CI, 2.8% to 4.0%) after 20 years of follow up. The risk of developing a CTGCT decreased with age (hazard ratio [HR], 0.93; 95% CI, 0.90 to 0.96), was lower after nonseminomatous germ cell tumor (HR, 0.58; 95% CI, 0.35 to 0.96) and decreased with every additional cycle of chemotherapy (HRper cycle, 0.74; 95% CI, 0.64 to 0.85). CONCLUSION: Approximately one in every 30 survivors of TGCT will develop a CTGCT, with CTGCT incidence increasing up to 20 years after a primary TGCT. Treatment with platinum-based chemotherapy shows a dose-dependent inverse association with CTGCT risk.

PORTEC-4a: international randomized trial of molecular profile-based adjuvant treatment for women with high-intermediate risk endometrial cancer.

BACKGROUND: Vaginal brachytherapy is currently recommended as adjuvant treatment in patients with high-intermediate risk endometrial cancer to maximize local control and has only mild side effects and no or limited impact on quality of life. However, there is still considerable overtreatment and also some undertreatment, which may be reduced by tailoring adjuvant treatment to the patients' risk of recurrence based on molecular tumor characteristics. PRIMARY OBJECTIVES: To compare the rates of vaginal recurrence in women with high-intermediate risk endometrial cancer, treated after surgery with molecular-integrated risk profile-based recommendations for either observation, vaginal brachytherapy or external pelvic beam radiotherapy or with standard adjuvant vaginal brachytherapy STUDY HYPOTHESIS: Adjuvant treatment based on a molecular-integrated risk profile provides similar local control and recurrence-free survival as current standard adjuvant brachytherapy in patients with high-intermediate risk endometrial cancer, while sparing many patients the morbidity of adjuvant treatment and reducing healthcare costs. TRIAL DESIGN: A multicenter, international phase III randomized trial (2:1) of molecular-integrated risk profile-based adjuvant treatment (experimental arm) or adjuvant vaginal brachytherapy (standard arm). MAJOR INCLUSION/EXCLUSION CRITERIA: Women aged 18 years and over with a histological diagnosis of high-intermediate risk endometrioid endometrial cancer after total abdominal or laparoscopic hysterectomy and bilateral salpingo-oophorectomy. High-intermediate risk factors are defined as: (i) International Federation of Gynecology and Obstetrics stage IA (with invasion) and grade 3; (ii) stage IB grade 1 or 2 with age ≥60 and/or lymph-vascular space invasion; (iii) stage IB, grade 3 without lymph-vascular space invasion; or (iv) stage II (microscopic and grade 1). ENDPOINTS: The primary endpoint is vaginal recurrence. Secondary endpoints are recurrence-free and overall survival; pelvic and distant recurrence; 5-year vaginal control (including treatment for relapse); adverse events and patient-reported symptoms and quality of life; and endometrial cancer-related healthcare costs. SAMPLE SIZE: 500 eligible and evaluable patients. ESTIMATED DATES FOR COMPLETING ACCRUAL AND PRESENTING RESULTS: Estimated date for completing accrual will be late 2021. Estimated date for presentation of (first) results is expected in 2023. TRIAL REGISTRATION: The trial is registered at clinicaltrials.gov (NCT03469674) and ISRCTN (11659025).

Impact of different adjuvant treatment approaches on survival in stage III endometrial cancer: A population-based study.

BACKGROUND: Patients with International Federation of Gynaecology and Obstetrics (FIGO) stage III endometrial cancer (EC) have a substantial risk of adverse outcomes. After surgery, adjuvant therapy is recommended with external beam radiotherapy (EBRT), chemotherapy (CT) or both EBRT and CT. Recent trials suggest that EBRT + CT is superior to EBRT or CT alone but also results in more toxicity. We have compared the outcome of different adjuvant treatments in a population-based cohort to identify subgroups that benefit most from EBRT + CT. METHODS: All patients diagnosed with FIGO stage III EC and treated with surgery in 2005-2016 were identified from the Netherlands Cancer Registry. The primary outcome was overall survival (OS); associations with adjuvant treatment were analysed using Cox regression analysis. RESULTS: Among 1241 eligible patients, EBRT + CT was associated with a better OS than CT (hazard ratio [HR] = 1.84, 95% confidence interval [CI] = 1.34-2.52) and EBRT alone (HR = 1.37, 95% CI = 1.05-1.79). In stage IIIC, there was a significant benefit of EBRT + CT compared with CT or EBRT alone. In stage IIIA-B, there was no difference between EBRT + CT or EBRT alone. In endometrioid EC (EEC) and carcinosarcomas, EBRT + CT was associated with a better OS than CT or EBRT alone. For uterine serous cancers, there was no survival benefit of EBRT + CT over CT. In all analysis by stage and histology, any adjuvant treatment was superior to no adjuvant therapy. CONCLUSIONS: In this population-based study, adjuvant EBRT + CT was associated with improved OS compared with CT or EBRT alone in FIGO stage IIIC EC, EEC and carcinosarcoma. This suggests that application of EBRT + CT in stage III should be further stratified according to these subgroups.

Platinum exposure and cause-specific mortality among patients with testicular cancer.

BACKGROUND: Although testicular cancer (TC) treatment has been associated with severe late morbidities, including second malignant neoplasms (SMNs) and ischemic heart disease (IHD), cause-specific excess mortality has been rarely studied among patients treated in the platinum era. METHODS: In a large, multicenter cohort including 6042 patients with TC treated between 1976 and 2006, cause-specific mortality was compared with general population mortality rates. Associations with treatment were assessed with proportional hazards analysis. RESULTS: With a median follow-up of 17.6 years, 800 patients died; 40.3% of these patients died because of TC. The cumulative mortality was 9.6% (95% confidence interval [CI], 8.5%-10.7%) 25 years after TC treatment. In comparison with general population mortality rates, patients with nonseminoma experienced 2.0 to 11.6 times elevated mortality from lung, stomach, pancreatic, rectal, and kidney cancers, soft-tissue sarcomas, and leukemia; 1.9-fold increased mortality (95% CI, 1.3-2.8) from IHD; and 3.9-fold increased mortality (95% CI, 1.5-8.4) from pneumonia. Seminoma patients experienced 2.5 to 4.6 times increased mortality from stomach, pancreatic, bladder cancer and leukemia. Radiotherapy and chemotherapy were associated with 2.1 (95% CI, 1.8-2.5) and 2.5 times higher SMN mortality (95% CI, 2.0-3.1), respectively, in comparison with the general population. In a multivariable analysis, patients treated with platinum-containing chemotherapy had a 2.5-fold increased hazard ratio (HR; 95% CI, 1.8-3.5) for SMN mortality in comparison with patients without platinum-containing chemotherapy. The HR for SMN mortality increased 0.29 (95% CI, 0.19-0.39) per 100 mg/m2 platinum dose administered (Ptrend  < .001). IHD mortality was increased 2.1-fold (95% CI, 1.5-4.2) after platinum-containing chemotherapy in comparison with patients without platinum exposure. CONCLUSIONS: Platinum-containing chemotherapy is associated with a dose-dependent increase in the risk of SMN mortality.

Risk of diabetes after para-aortic radiation for testicular cancer.

BACKGROUND: While the risk of diabetes is increased following radiation exposure to the pancreas among childhood cancer survivors, its association among testicular cancer (TC) survivors has not been investigated. METHODS: Diabetes risk was studied in 2998 1-year TC survivors treated before 50 years of age with orchidectomy with/without radiotherapy between 1976 and 2007. Diabetes incidence was compared with general population rates. Treatment-specific risk of diabetes was assessed using a case-cohort design. RESULTS: With a median follow-up of 13.4 years, 161 TC survivors were diagnosed with diabetes. Diabetes risk was not increased compared to general population rates (standardised incidence ratios (SIR): 0.9; 95% confidence interval (95% CI): 0.7-1.1). Adjusted for age, para-aortic radiotherapy was associated with a 1.66-fold (95% CI: 1.05-2.62) increased diabetes risk compared to no radiotherapy. The excess hazard increased with 0.31 with every 10 Gy increase in the prescribed radiation dose (95% CI: 0.11-0.51, P = 0.003, adjusted for age and BMI); restricted to irradiated patients the excess hazard increased with 0.33 (95% CI: -0.14 to 0.81, P = 0.169) with every 10 Gy increase in radiation dose. CONCLUSION: Compared to surgery only, para-aortic irradiation is associated with increased diabetes risk among TC survivors.

Risk of Solid Cancer After Treatment of Testicular Germ Cell Cancer in the Platinum Era.

Purpose Testicular cancer (TC) treatment increases risk of subsequent malignant neoplasms (SMNs). It is unknown whether changes in TC treatment over time have affected SMN risk. Methods Solid SMN risk was evaluated in a multicenter cohort comprising 5,848 1-year survivors treated for TC before age 50 years between 1976 and 2007. SMN incidence was compared with cancer incidence in the general population. Treatment-specific risks were assessed using multivariable regression in a case-cohort design. Results After a median follow-up of 14.1 years, 350 solid SMNs were observed, translating into a 1.8-fold (95% CI, 1.6-2.0) increased risk compared with general population rates. Solid SMN risk was increased in patients with seminoma and those with nonseminoma (standardized incidence ratio, 1.52 and 2.21, respectively). Patients with nonseminoma experienced increased risk of SMNs of the thyroid, lung, stomach, pancreas, colon, and bladder and of melanoma and soft tissue sarcoma, whereas those with seminoma experienced increased risk of SMNs of the small intestine, pancreas, and urinary bladder. The 25-year cumulative incidence of solid SMNs was 10.3% (95% CI, 9.0% to 11.6%). In multivariable analysis, platinum-based chemotherapy was associated with increased risk of a solid SMN (hazard ratio [HR], 2.40; 95% CI, 1.58 to 3.62), colorectal SMN (HR, 3.85; 95% CI, 1.67 to 8.92), and noncolorectal GI SMN (HR, 5.00; 95% CI, 2.28 to 10.95). Receipt of platinum 400 to 499 and ≥ 500 mg/m2 increased solid SMN risk compared with surgery only (HR, 2.43; 95% CI, 1.40 to 4.23 and HR, 2.42; 95% CI, 1.50 to 3.90, respectively), whereas risk was not significantly increased with lower doses (HR, 1.75; 95% CI, 0.90 to 3.43). The HR of a GI SMN increased by 53% (95% CI, 26% to 80%) per 100 mg/m2 of platinum-containing chemotherapy. The HR of an infradiaphragmatic SMN increased by 8% per Gray of radiation dose administered (95% CI, 6% to 9%; P < .001). Conclusion Radiotherapy and platinum-containing chemotherapy are associated with increased solid SMN risk, specifically with GI SMNs.

Impact of brachytherapy technique (2D versus 3D) on outcome following radiotherapy of cervical cancer.

Purpose: The purpose of this study was to analyze the effect of 2D conventional brachytherapy (CBT) compared to 3D MRI-guided brachytherapy (IGBT) with and without the use of interstitial needles on local control, overall survival, and toxicity in patients treated for cervical cancer with radiation or chemoradiation. Material and methods: A retrospective analysis was performed of biopsy-proven FIGO IB-IVA cervical cancer patients, treated with primary radiation or chemoradiation, followed by brachytherapy (BT) between January 1997 and July 2016. Endpoints were local control, overall survival, and toxicity. Results: Of 126 patients included, 35 have been treated with CBT, 31 with IGBT without needles (IC), and 60 with IGBT with needles (ICIS). External beam radiotherapy (EBRT) had mostly been delivered concurrently with chemotherapy (weekly cisplatin). Overall local control was 93% after 1 year, and 88% after 3 years. Overall 3-year survival was 75%, and 5-year survival was 66%. The 3D technique (IGBT cohorts) showed a trend for an improved local control and overall survival (p = 0.05) compared to the 2D technique (CBT cohort). A decrease in toxicity was observed from 17% (2D cohort) to 12% (3D cohort). The use of interstitial needles was associated with a higher high-risk clinical target volume (HR-CTV) dose (11.3 Gy vs. 9.9 Gy) and a lower D2cc bladder dose (10.9 Gy vs. 14.7 Gy, both p < 0.01). Conclusions: In cervical cancer treatment, the use of a 3D brachytherapy technique (MRI-guided with or without interstitial needles) showed a trend towards an increased local control and improved overall survival with reduced toxicity, compared to the conventional 2D brachytherapy technique. The use of interstitial needles allowed dose sculpting, resulting in delivery of higher doses to the HR-CTV, while reducing radiation doses to organs at risk, such as the bladder.

Radiation therapy combined with hyperthermia versus cisplatin for locally advanced cervical cancer: Results of the randomized RADCHOC trial.

BACKGROUND: Chemoradiation (RT-CT) is standard treatment for locally advanced cervical cancer (LACC). This study tried to establish if radiotherapy combined with hyperthermia (RT-HT) should be preferred in bulky and/or FIGO-stage ⩾III. METHODS: In this open-label, multicenter randomized trial, patients with LACC were randomly assigned by a computer-generated, biased coin minimization technique to RT-CT or RT-HT. Central randomization was done with stratification by FIGO-stage, tumour diameter and nodal status. Primary endpoint was event free survival (EFS). Secondary endpoints were pelvic recurrence free survival (PRFS), overall survival (OS) and treatment related toxicity. Analysis was done by intention to treat. RESULTS: The trial was closed prematurely (87 of 376 planned patients enrolled: 43 RT-CT; 44 RT-HT). Median follow-up time was 7.1 years. The cumulative incidence of an event was 33% in the RT-CT group and 35% in the RT-HT group. The corresponding hazard rate (HR) for EFS was 1.15 (CI: 0.56-2.36, p=0.7). Also the hazards for PRFS (0.94; CI 0.36-2.44) and OS (1.04; CI 0.48-2.23) at 5 years were comparable between both treatment arms as was grade ⩾3 radiation related late toxicity (6 RT-CT and 5 RT-HT patients). CONCLUSION: After 25% of intended accrual, data suggest comparable outcome for RT-CT and RT-HT.

Local Recurrence in the Lateral Lymph Node Compartment: Improved Outcomes with Induction Chemotherapy Combined with Multimodality Treatment.

BACKGROUND: Lateral nodal disease is of major importance in the treatment of rectal cancer in the East, but a mostly neglected entity in the West. In this article, the treatment of recurrences in the lateral compartment (latLRs) in a national tertiary referral center is evaluated. METHODS: Of 214 patients with locally recurrent rectal cancer who underwent multimodality treatment in the Catharina Hospital in the last 10 years, a total of 51 patients with latLR were selected (the latLR region was classified as upper, middle, or lower). Thirteen (25 %) of these patients underwent induction chemotherapy (ICT) prior to chemo(re)irradiation. RESULTS: LatLRs occurred mainly after low and N+ primary tumors. Seven (14 %) patients had a complete response (pCR) and 28 (55 %) underwent an R0 resection. Patients with a lower latLR had the highest chance of undergoing an abdominoperineal resection and resection of anterior organs. ICT resulted in a 31 % pCR rate compared with 8 % without ICT (p = 0.039). Patients who received ICT had an 85 % R0 resection rate, while this was 45 % in patients who did not receive ICT (p = 0.013). The 5-year local re-recurrence (LRR) rate was 64.3 %, and overall survival (OS) was 34.2 %; the only factor improving these was an R0 resection. Five-year survival after multivariate analyses was 10.3 % after an R+ resection compared with 66.8 % after an R0 resection (p = 0.011). CONCLUSIONS: LatLRs impose a major surgical challenge and result in high LRR and low OS. More R0 resections can possibly be achieved with ICT, which is the only factor that can improve LRR and OS.

Results of intraoperative electron beam radiotherapy containing multimodality treatment for locally unresectable T4 rectal cancer: a pooled analysis of the Mayo Clinic Rochester and Catharina Hospital Eindhoven.

BACKGROUND: The aim of this study is to analyse the pooled results of intraoperative electron beam radiotherapy (IOERT) containing multimodality treatment of locally advanced T4 rectal cancer, initially unresectable for cure, from the Mayo Clinic, Rochester, USA (MCR) and Catharina Hospital, Eindhoven, The Netherlands (CHE), both major referral centers for locally advanced rectal cancer. A rectal tumor is called locally unresectable for cure if after full clinical work-up infiltration into the surrounding structures or organs has been demonstrated, which would result in positive surgical margins if resection was the initial component of treatment. This was the reason to refer these patients to the IOERT program of one of the centers. METHODS: In the period from 1981 to 2010, 417 patients with locally unresectable T4 rectal carcinomas at initial presentation were treated with multimodality treatment including IOERT at either one of the two centres. The preferred treatment approach was preoperative (chemo) radiation and intended radical surgery combined with IOERT. Risk factors for local recurrence (LR), cancer specific survival, disease free survival and distant metastases (DM) were assessed. RESULTS: A total of 306 patients (73%) underwent a R0 resection. LRs and metastases occurred more frequently after an R1-2 resection (P<0.001 and P<0.001 respectively). Preoperative chemoradiation (preop CRT) was associated with a higher probability of having a R0 resection. Waiting time after preoperative treatment was inversely related with the chance of developing a LR, especially after R+ resection. In 16% of all cases a LR developed. Five-year disease free survival and overall survival (OS) were 55% and 56% respectively. CONCLUSIONS: An acceptable survival can be achieved in treatment of patients with initially unresectable T4 rectal cancer with combined modality therapy that includes preop CRT and IOERT. Completeness of the resection is the most important predictive and prognostic factor in the treatment of T4 rectal cancer for all outcome parameters. IOERT can reduce the LR rate effectively, especially in R+ resected patients.

[Breast-conserving surgery and radiotherapy as a one-day procedure]. / Borstsparende ingreep en bestraling in dagbehandeling.

A single dose of irradiation to the lumpectomy cavity alone after breast-conserving surgery in breast cancer patients has been available in the Netherlands since 2011. This new treatment modality is used in the Haaglanden Medical Centre in The Hague and in the Catharina Hospital in Eindhoven. The goal of intraoperative radiation therapy is to limit the patient burden caused by whole breast irradiation, while maintaining excellent local tumour control. The technique is used only in patients with a low probability of recurrent disease in the breast. Approximately 150 patients receive intraoperative radiation therapy each year In the Netherlands, an estimated 4,000 breast cancer patients were eligible in 2013 for this new treatment technique or another method of partial breast irradiation. In both hospitals the results are closely monitored. Only 15 of the first 200 patients experienced a side effect within a period of 3 months after intraoperative radiation therapy. These side effects were successfully treated either with antibiotics or with surgery.

Radicality of resection and survival after multimodality treatment is influenced by subsite of locally recurrent rectal cancer.

PURPOSE: To analyze results of multimodality treatment in relation to subsite of locally recurrent rectal cancer (LRRC). METHOD AND MATERIALS: A total of 170 patients with LRRC who underwent treatment between 1994 and 2008 were studied. The basic principle of multimodality treatment was preoperative (chemo)radiotherapy, intended radical surgery, and intraoperative radiotherapy. The subsites of LRRC were classified as presacral, posterolateral, (antero)lateral, anterior, anastomotic, or perineal. Subsites were related to radicality of the resection, local re-recurrence rate, distant metastasis rate, and cancer-specific survival. RESULTS: R0 resections were achieved in 54% of the patients, and 5-year cancer-specific survival was 40.5%. The worst outcomes were seen in presacral LRRC, with only 28% complete resections and 19% 5-year survival (p = 0.03 vs. other subsites). Anastomotic LRRC resulted in the most favorable outcomes, with 77% R0 resections and 60% 5-year survival (p = 0.04). Generally, if a complete resection was achieved, survival improved, except in posterolateral LRRC. Local re-recurrence and metastasis rate were lowest in anastomotic LRRC. CONCLUSIONS: Classification of the subsite of LRRC is a predictor of potentially resectable and consequently curable disease. Treatment of posterior LRRC imposes poor results, whereas anastomotic LRRC location shows superior results.

Patterns of local recurrence in locally advanced rectal cancer after intra-operative radiotherapy containing multimodality treatment.

BACKGROUND AND PURPOSE: The purpose of this study is to analyze the patterns of local recurrence (LR) after intra-operative radiotherapy (IORT) containing multimodality treatment of locally advanced rectal carcinoma (LARC). METHODS AND MATERIALS: Two hundred and ninety patients with LARC who underwent multimodality treatment between 1994 and 2006 were studied. For patients who developed LR, the subsite was classified into presacral, postero-lateral, lateral, anterior, anastomotic or perineal. Patient and treatment characteristics were related to subsite of LR. RESULTS: After 5years, 34 patients (13.2%) developed LR. The most prominent subsite of LR was the presacral subsite. 47% of the local recurrences occurred outside the IORT field. Most recurrences developed when IORT was given dorsally, while least occurred when IORT was given ventrally. Especially after dorsal IORT a high amount of infield recurrences were observed (6 of 8; 75%). In multi-variate analysis tumor distance of more than 5cm from the anal verge and a positive circumferential margin were associated with presacral local recurrence. CONCLUSIONS: Multimodality treatment is effective in the prevention of local recurrence in LARC. IORT application to the area most at risk is feasible and seems effective in the prevention of local recurrence. Dorsal tumor location results in unfavourable oncologic results.

Radical resection after IORT-containing multimodality treatment is the most important determinant for outcome in patients treated for locally recurrent rectal cancer.

BACKGROUND: The optimal treatment for locally recurrent rectal cancer (LRRC) is still a matter of debate. This study assessed the outcome of LRRC patients treated with multimodality treatment, consisting of neoadjuvant radio (chemo-) therapy, extended resection, and intraoperative radiotherapy. METHODS: One hundred and forty-seven consecutive patients with LRRC who underwent treatment between 1994 and 2006 were studied. The prognostic values of patient-, tumor- and treatment-related characteristics were tested with uni- and multivariate analysis. RESULTS: Median overall survival was 28 months (range 0-146 months). Five-year overall, disease-free, and metastasis-free survival and local control (OS, DFS, MFS, and LC respectively) were 31.5%, 34.1%, 49.5% and 54.1% respectively. Radical resection (R0) was obtained in 84 patients (57.2%), microscopically irradical resection (R1) in 34 patients (23.1%), and macroscopically irradical resection (R2) in 29 patients (19.7%). For patients with a radical resection median OS was 59 months and the 5-year OS, DFS, MFS, and LC were 48.4%, 52.3%, 65.5% and 68.9%, respectively. Radical resection was significantly correlated with improved OS, DFS, and LC (P < 0.001). Patients who received re-irradiation or full-course radiotherapy survived significantly longer (P = 0.043) and longer without local recurrence (P = 0.038) or metastasis (P < 0.001) compared to patients who were not re-irradiated. CONCLUSIONS: Radical resection is the most significant predictor of improved survival in patients with LRRC. Neoadjuvant radio (chemo-) therapy is the best option in order to realize a radical resection. Re-irradiation is feasible in patients who already received irradiation as part of the primary rectal cancer treatment.

What CTV-to-PTV margins should be applied for prostate irradiation? Four-dimensional quantitative assessment using model-based deformable image registration techniques.

PURPOSE: To quantify adequate anisotropic clinical target volume (CTV)-to-planning target volume (PTV) margins for three different setup strategies used during prostate irradiation: (1) no setup corrections, (2) on-line corrections determined from bony anatomy, and (3) on-line corrections determined from gold markers. METHOD AND MATERIALS: Three radiation oncologists independently delineated the CTV on computed tomography images of 30 prostate cancer patients. Eight repeat scans were acquired to allow simulation of the delivered dose distributions in changing geometry. Different registration approaches were taken to mimic the different setup strategies. A surface model-based deformable image registration system was used to warp the delivered dose distributions back to the dose in the planning computed tomography scan. On the basis of the geometric extent of the underdosed areas, a set of anisotropic margins was derived to ensure a minimal dose to the CTV of 95% for 90% of the patients. RESULTS: Without setup correction, margins of approximately 11 mm for the corpus of the prostate and 15 mm for the seminal vesicles were required. These margins could be reduced to 8 and 13 mm when aligning the patient to the bony anatomy and to 3 and 8 mm aligning the patient to implanted gold markers. A larger margin at the apex was required to account for the significant observer variability and steep dose gradients at this location (11 mm using skin marker registration, 9 mm using bony anatomy registration, and 6 mm using gold marker registration). CONCLUSIONS: Novel voxel tracking techniques have enabled us to calculate accumulated dose distributions and design accurate three-dimensional CTV-to-PTV margins for prostate irradiation.

Impact of external beam adjuvant radiotherapy on health-related quality of life for long-term survivors of endometrial adenocarcinoma: a population-based study.

PURPOSE: To compare the health-related quality of life (HRQOL) among 5-10-year survivors of Stage I-II endometrial (adeno-)carcinoma (EC) treated with surgery alone or surgery with external beam adjuvant radiotherapy (EBRT) and an age-matched norm population. METHODS AND MATERIALS: A population-based, cross-sectional survey was conducted by the Eindhoven Cancer Registry. All patients were included who had been diagnosed with EC between 1994 and 1998 (n = 462). Information from the questionnaires returned was linked to data from the Eindhoven Cancer Registry on patient, tumor, and treatment characteristics. RESULTS: Responses were received from 75% of the patients. The analyses were restricted to women with Stage I-II disease at diagnosis, treated with either surgery alone or surgery with adjuvant EBRT, and without recurrent disease or new primary malignancies (n = 264). The patients who had received adjuvant EBRT (n = 80) had had a significantly higher tumor stage and grade at diagnosis (p < 0.0001) and a longer mean time since diagnosis (p = 0.04). Age, number of comorbid diseases, current marital status, nulliparity, education, and occupation were similar for both treatment groups. On multivariate analyses, adjuvant EBRT was independently and negatively associated with the vitality and physical and social well-being scale scores. The HRQOL scores of both treatment groups, however, were similar to those of an age-matched norm population. CONCLUSION: In general, the HRQOL of EC survivors is good. EC survivors treated with surgery alone had a better HRQOL than women treated with surgery and adjuvant EBRT, although for both groups, the HRQOL was in the range of the norm population.

Dosimetric comparison of interactive planned and dynamic dose calculated prostate seed brachytherapy.

PURPOSE: To compare the dosimetrical results of an interactive planning procedure and a procedure based on dynamic dose calculation for permanent prostate brachytherapy. MATERIALS AND METHODS: Between 6/2000 and 11/2005, 510 patients underwent (125)I implants for T1-T2 prostate cancer. Before 4/2003, 187 patients were treated using an interactive technique that included needle updating. After that period, 323 patients were treated with a more refined dynamic technique that included constant updating of the deposited seed position. The comparison is based on postimplant dose - volume parameters such as the V(100) and d(90) for the target, V(100)(r) for the rectum and d(10)(u) for the urethra. Furthermore, the target volume ratios (TVR identical with V(100)(body)/V(100)), and the homogeneity indices (HI identical with [V(100)-V(150)]/V(100)) were calculated as additional quality parameters. RESULTS: The dose outside the target volume was significantly reduced, the V(100)(r) decreased from 1.4 cm(3) for the interactive technique to 0.6 cm(3) for the dynamic technique. Similarly the mean TVR reduced from 1.66 to 1.44. In addition, the mean V(100) increased from 92% for the interactive procedure to 95% for the dynamic procedure. More importantly, the percentage of patients with a V(100) < 80% reduced from 5% to 1%. A slight decline was observed with regard to the d(10)(u) (136% vs. 140%) and the HI (0.58 vs. 0.51). CONCLUSION: The dynamic implant procedure resulted in improved implants. Almost ideal dose coverage was achieved, while minimizing the dose outside the prostate.