In vivodosimetry in cancer patients undergoing intraoperative radiation therapy.

In vivodosimetry (IVD) is an important tool in external beam radiotherapy (EBRT) to detect major errors by assessing differences between expected and delivered dose and to record the received dose by individual patients. Also, in intraoperative radiation therapy (IORT), IVD is highly relevant to register the delivered dose. This is especially relevant in low-risk breast cancer patients since a high dose of IORT is delivered in a single fraction. In contrast to EBRT, online treatment planning based on intraoperative imaging is only under development for IORT. Up to date, two commercial treatment planning systems proposed intraoperative ultrasound or in-room cone-beam CT for real-time IORT planning. This makes IVD even more important because of the possibility for real-time treatment adaptation. Here, we summarize recent developments and applications of IVD methods for IORT in clinical practice, highlighting important contributions and identifying specific challenges such as a treatment planning system for IORT. HDR brachytherapy as a delivery technique was not considered. We add IVD for ultrahigh dose rate (FLASH) radiotherapy that promises to improve the treatment efficacy, when compared to conventional radiotherapy by limiting the rate of toxicity while maintaining similar tumour control probabilities. To date, FLASH IORT is not yet in clinical use.

Coverage of Lateral Lymph Nodes in Rectal Cancer Patients with Routine Radiation Therapy Practice and Associated Locoregional Recurrence Rates.

PURPOSE: Involved internal iliac and obturator lateral lymph nodes (LLNs) are a known risk factor for the occurrence of ipsilateral local recurrences (LLR) in rectal cancer. This study examined coverage of LLNs with routine radiation therapy practice in the Netherlands and associated LLR rates. METHODS AND MATERIALS: Patients with a primary tumor ≤8 cm of the anorectal junction, cT3-4 stage, and at least 1 internal iliac or obturator LLN with short axis ≥5 mm who received neoadjuvant (chemo)radiation therapy, were selected from a national, cross-sectional study of patients with rectal cancer treated in the Netherlands in 2016. Magnetic resonance images and radiation therapy treatment plans were reviewed regarding segmented LLNs as gross tumor volume (GTV), location of LLNs within clinical target volume (CTV), and received proportion of the planned radiation therapy dose. RESULTS: A total of 223 out of 3057 patients with at least 1 LLN ≥5 mm were selected. Of those, 180 (80.7%) LLNs were inside the CTV, of which 60 (33.3%) were segmented as GTV. Overall, 202 LLNs (90.6%) received ≥95% of the planned dose. Four-year LLR rates were not significantly higher for LLNs situated outside the CTV compared with those inside (4.0% vs 12.5%, P = .092) or when receiving <95% versus ≥95% of the planned radiation therapy dose (7.1% vs 11.3%, P = .843), respectively. Two of 7 patients who received a dose escalation of 60 Gy developed an LLR (4-year LLR rate of 28.6%). CONCLUSIONS: This evaluation of routine radiation therapy practice showed that adequate coverage of LLNs was still associated with considerable 4-year LLR rates. Techniques resulting in better local control for patients with involved LLNs need to be explored further.

Development of a consensus-based delineation guideline for locally recurrent rectal cancer.

BACKGROUND AND PURPOSE: Neoadjuvant chemoradiotherapy (nCRT) is used in locally recurrent rectal cancer (LRRC) to increase chances of a radical surgical resection. Delineation in LRRC is hampered by complex disease presentation and limited clinical exposure. Within the PelvEx II trial, evaluating the benefit of chemotherapy preceding nCRT for LRRC, a delineation guideline was developed by an expert LRRC team. MATERIALS AND METHODS: Eight radiation oncologists, from Dutch and Swedish expert centres, participated in two meetings, delineating GTV and CTV in six cases. Regions at-risk for re-recurrence or irradical resection were identified by eleven expert surgeons and one expert radiologist. Target volumes were evaluated multidisciplinary. Inter-observer variation was analysed. RESULTS: Inter-observer variation in delineation of LRRC appeared large. Multidisciplinary evaluation per case is beneficial in determining target volumes. The following consensus regarding target volumes was reached. GTV should encompass all tumour, including extension into OAR if applicable. If the tumour is in fibrosis, GTV should encompass the entire fibrotic area. Only if tumour can clearly be distinguished from fibrosis, GTV may be reduced, as long as the entire fibrotic area is covered by the CTV. CTV is GTV with a 1 cm margin and should encompass all at-risk regions for irradical resection or re-recurrence. CTV should not be adjusted towards other organs. Multifocal recurrences should be encompassed in one CTV. Elective nodal delineation is only advised in radiotherapy-naïve patients. CONCLUSION: This study provides a first consensus-based delineation guideline for LRRC. Analyses of re-recurrences is needed to understand disease behaviour and to optimize delineation guidelines accordingly.

The Dutch-Belgian Registry of Stereotactic Body Radiation Therapy for Liver Metastases: Clinical Outcomes of 515 Patients and 668 Metastases.

PURPOSE: Although various studies have reported that stereotactic body radiation therapy (SBRT) for liver metastases has high local control rates and relatively low toxicity, most series included a small number of patients. We aimed to validate these outcomes in a large multi-institution patient cohort treated in accordance with a common protocol. METHODS AND MATERIALS: A shared web-based registry of patients with liver metastases treated with SBRT was developed by 13 centers (12 in the Netherlands and 1 in Belgium). All the centers had previously agreed on the items to be collected, the fractionation schemes, and the organs-at-risk constraints to be applied. Follow-up was performed at the discretion of the centers. Patient, tumor, and treatment characteristics were entered in the registry. Only liver metastases treated individually as independent targets and with at least 1 radiologic follow-up examination were considered for local control analysis. Toxicity of grade 3 or greater was scored according to the Common Terminology Criteria of Adverse Events (v4.03). RESULTS: Between January 1, 2013, and July 31, 2019, a total of 515 patients were entered in the web-based registry. The median age was 71 years. In total, 668 liver metastases were registered, and 447 were included for local control analysis. The most common primary tumor origin was colorectal cancer (80.3%), followed by lung cancer (8.9%) and breast cancer (4%). The most-used fractionation scheme was 3x18-20 Gy (36.0%), followed by 8x7.5 Gy (31.8%), 5x11-12 Gy (25.5%), and 12x5 Gy (6.7%). The median follow-up time was 1.1 years for local control and 2.3 years for survival. Actuarial 1-year local control was 87%; 1-year overall survival was 84%. Toxicity of grade 3 or greater was found in 3.9% of the patients. CONCLUSIONS: This multi-institutional study confirms the high rates of local control and limited toxicity in a large patient cohort. Stereotactic body radiation therapy should be considered a valuable part of the multidisciplinary approach to treating liver metastases.

Patient explicit consideration of tradeoffs in decision making about rectal cancer treatment: benefits for decision process and quality of life.

Introduction: Patient preferences are often not discussed in treatment decisions in oncology. We introduced an online values clarification method (VCM) to help newly diagnosed rectal cancer patients participate in shared decision making about short-course preoperative radiotherapy. Material and Methods: We offered a link to the VCM to a subset of consecutive patients before the pretreatment consultation with the radiation oncologist. Consultations were audiotaped and coded for expressions of patient preferences. Patients were asked to complete pre- and post-consultation questionnaires. Questionnaires assessed values clarity, decision regret and presence and impact of fecal incontinence and sexual problems. Results: Of 135 patients who had their consultation audiotaped and completed questionnaires, 35 received and accessed the VCM-link. Patients in the VCM-group slightly more often expressed preferences during consultations. Questionnaire data showed that patients in the VCM-group did not differ in how clear their values were, but experienced lower regret and less impact of treatment harms at 6 months follow-up; differences were non-significant but in the same direction at 12 months. Discussion: This is the first study to assess the effect of an adaptive conjoint analysis-based VCM on actual patient-clinician communication, and long-term decision regret and impact of treatment harms. Being explicitly invited to think about treatment benefits and harms seems to help patients to live with treatment consequences.

Small Cell Carcinoma of the Esophagus: A Nationwide Analysis of Treatment and Outcome at Patient Level in Locoregional Disease.

BACKGROUND AND PURPOSE: Small cell carcinoma of the esophagus (SCEC) is a rare subtype of esophageal cancer for which optimal treatment is unknown. We analyzed the impact of treatment factors on outcome in patients with nonmetastasized SCEC. METHODS: Patients with a histologically confirmed SCEC without distant metastases were analyzed in a nationwide multicenter retrospective cohort. All patients received radiotherapy as part of curative treatment between January 2000 and December 2014. Details on treatment and outcome were retrieved from individual charts. Cox regression analysis was used to determine prognostic factors for survival. RESULTS: Fifty-eight patients were analyzed. Median survival was 16 months (95% confidence interval, 11-21 mo). Infield recurrences occurred in 25%, distant metastases in 45%, and brain metastases in 12%. In total, 63% of patients developed a recurrence. Most recurrences (67%) occurred within 1 year. In univariable analyses an increased number of chemotherapy cycles (>3) and lower radiotherapy doses (<45 Gy) were associated with improved survival. T-stage, N-stage, treatment period, type of chemotherapy, prophylactic cranial irradiation, and age were not associated with survival. In multivariable analyses, only the number of chemotherapy cycles was associated with better survival (hazard ratio, 0.78; P=0.006). CONCLUSIONS: SCEC recurs frequently at distant sites after definitive chemoradiotherapy and usually within 1 year after curative treatment. With a dose of 45 to 50 Gy, infield recurrence rate was low. We found a relationship between number of received chemotherapy cycles and survival with best results obtained after at least 4 cycles of chemotherapy.

Breath-hold versus mid-ventilation in SBRT of adrenal metastases.

PURPOSE: To improve local control in radiotherapy of adrenal metastases precise dose delivery without increasing toxicity is vital. Decreasing the Clinical Target Volume (CTV) - Planning Target Volume (PTV) margins by reducing breathing movement can achieve this. Few data were published concerning the effect of a breath-hold technique. This study investigates the potential of Active Breathing Control (ABC) to limit adrenal breathing movement and reduce CTV-PTV margins. METHODS: We compared adrenal gland movement in free-breathing, making use of the Mid-ventilation (MidV) technique, and with ABC. The coordinates of the adrenal glands obtained on ten phases of a free breathing 4D-CT and on several repeat inspiration ABC CT-scans were measured. Separate coordinates, the random margin component and the margin vector norm were computed and compared between the two techniques. RESULTS: We compared the two techniques in 11 patients (21 adrenal glands) and found the largest movement in the Z-direction, with values of 8.7 ±â€¯4.2 mm for MidV and 2.4 ±â€¯1.5 mm for ABC. In 71% of the cases ABC resulted in a smaller margin component than MidV, although non-significant (p ≥ 0.4). CONCLUSION: Movement of the adrenal gland is largest in the Z-direction. The mean difference in the margin vector norm between both techniques was small with large variations over the patient group, the clinical effect of these differences is unknown. Applying an individualised motion management strategy could be beneficial. If a peak-to-peak amplitude above 15 mm in the Z-direction is observed in the MidV scan we advise to examine if a breath-hold technique could reduce margins.

Long-Term Health-Related Quality of Life in Patients With Rectal Cancer After Preoperative Short-Course and Long-Course (Chemo) Radiotherapy.

BACKGROUND: Both preoperative short-course radiotherapy (SC-PRT) and preoperative long-course chemo radiotherapy (CRT) have shown to reduce local recurrence rates after total mesorectal excision (TME), but neither resulted in improved survival. This study compared the long-term health-related quality of life (HRQL) and symptoms between CRT and SC-PRT. METHODS: Patients who were preoperatively treated with a total dose of 50.0 to 50.4 Gy for locally advanced rectal cancers were identified from 2 hospital registries. Starting from 2011, all patients who were disease-free in the study population (n = 105) were sent a HRQL-questionnaire composed of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and questions on bowel and urinary function. Patients who underwent SC-PRT in the TME trial were used as a reference group. RESULTS: HRQL results from 85 patients receiving CRT (81.0%), with a median follow-up time of 58 months, were compared with the results of patients who underwent SC-PRT (n = 306). Apart from more nausea and vomiting reported by patients receiving CRT (mean score for CRT 5.9 vs. 1.3 for SC-PRT; P < .01; not clinically relevant) and less satisfaction with urinary function indicated by patients who received CRT (mean score for CRT 71.2 vs. 81.2 for SC-PRT; P < .01), no significant differences were found in HRQL and symptoms between patients who received CRT and SC-PRT. CONCLUSIONS: This analysis of HRQL in patients who received CRT shows no clinically relevant differences in long-term HRQL and symptoms between patients who received CRT and SC-PRT, apart from less satisfaction with urinary function reported by patients who received CRT. These results indicate that both approaches have a comparable impact on long-term HRQL.

[Decision-making in preoperative radiotherapy in rectal cancer: variation in provision of information]. / Besluitvorming over preoperatieve radiotherapie bij rectumcarcinoom: Variatie in de informatievoorziening.

OBJECTIVE: To investigate the information provision concerning possible benefits and harms of short-course preoperative radiotherapy (PRT) at pre-treatment consultations between radiation oncologists and rectal cancer patients. DESIGN: Observational study. METHOD: We audiotaped the consultations between 17 radiation oncologists and 81 patients with primary rectal cancer who were eligible for PRT. The recordings were transcribed and analysed descriptively. RESULTS: A median of seven benefits/harms of PRT were addressed at each consultation (range, 2-13). This number differed both in and between individual oncologists and was not consistently associated with the patient's characteristics. A total of 30 different treatment outcomes was addressed. The effect of PRT on local control was addressed in all consultations, and the effect on survival in 16%. The most important adverse effects according to the literature are bowel dysfunction and sexual dysfunction. These were addressed in 82% and 85% of consultations, respectively; sexual problems were discussed significantly more often with male than female patients. Four out of five patients did not initiate discussion on potential benefits/harms. CONCLUSION: There was a considerable variation in the number and nature of benefits and harms of PRT that were discussed prior to treatment. This variation indicates a lack of clarity concerning which benefits/harms of radiotherapy should be discussed with newly-diagnosed patients. This suboptimal provision of information to patients hampers the process of shared decision making, in which the decision is based on each individual patient's weighing of benefits and harms. We do not believe our findings to be specific for PRT, but expect to find similar variation in provision of information with regard to other treatment decisions.

Acute toxicity after a diverting stoma and spacer prior to chemoradiation in locally advanced rectal cancer.

BACKGROUND AND PURPOSE: Chemoradiotherapy (CRT) followed by surgery is the standard of care for locally advanced rectal cancer (LARC). For grade ⩾3 acute diarrhea there is a relationship between dose and irradiated small bowel volume. The aim of this study was to evaluate whether combined placement of a diverting stoma and sigmoid spacer (DSSS) led to reduced irradiated small bowel volume and less grade ⩾3 acute diarrhea in the treatment of LARC. MATERIALS/METHODS: Between 2003 and 2010, 54 of 189 LARC patients treated with CRT in two institutions had a DSSS prior to CRT. Data on patient and treatment characteristics and outcomes were collected retrospectively. Delineation of small bowel was performed with planning CT-scans. CTCAE version 4.0 was used for acute toxicity. RESULTS: Patients with a DSSS had significantly less small bowel volume irradiated up to doses of 20Gy. This difference was not observed for the higher dose levels. CRT induced grade ⩾3 acute diarrhea was not different between the two groups (8.3% vs. 12.8%; p=0.41). CONCLUSION: DSSS is not clearly beneficial to reduce grade ⩾3 acute diarrhea, and it must be considered whether placement of a DSSS is justified for this purpose.

Target volume delineation variation in radiotherapy for early stage rectal cancer in the Netherlands.

PURPOSE: The aim of this study was to measure and improve the quality of target volume delineation by means of national consensus on target volume definition in early-stage rectal cancer. METHODS AND MATERIALS: The CTV's for eight patients were delineated by 11 radiation oncologists in 10 institutes according to local guidelines (phase 1). After observer variation analysis a workshop was organized to establish delineation guidelines and a digital atlas, with which the same observers re-delineated the dataset (phase 2). Variation in volume, most caudal and cranial slice and local surface distance variation were analyzed. RESULTS: The average delineated CTV volume decreased from 620 to 460 cc (p<0.001) in phase 2. Variation in the caudal CTV border was reduced significantly from 1.8 to 1.2 cm SD (p=0.01), while it remained 0.7 cm SD for the cranial border. The local surface distance variation (cm SD) reduced from 1.02 to 0.74 for anterior, 0.63 to 0.54 for lateral, 0.33 to 0.25 for posterior and 1.22 to 0.46 for the sphincter region, respectively. CONCLUSIONS: The large variation in target volume delineation could significantly be reduced by use of consensus guidelines and a digital delineation atlas. Despite the significant reduction there is still a need for further improvement.