[18F]FDG-PET-Based Personalized Radiotherapy Dose Prescription.

PET imaging with 2'-deoxy-2'-[18F]fluoro-D-glucose ([18F]FDG) has become one of the pillars in the management of malignant diseases. It has proven value in diagnostic workup, treatment policy, follow-up, and as prognosticator for outcome. [18F]FDG is widely available and standards have been developed for PET acquisition protocols and quantitative analyses. More recently, [18F]FDG-PET is also starting to be appreciated as a decision aid for treatment personalization. This review focuses on the potential of [18F]FDG-PET for individualized radiotherapy dose prescription. This includes dose painting, gradient dose prescription, and [18F]FDG-PET guided response-adapted dose prescription. The current status, progress, and future expectations of these developments for various tumor types are discussed.

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.

Circulating tumor DNA detection after neoadjuvant treatment and surgery predicts recurrence in patients with early-stage and locally advanced rectal cancer.

INTRODUCTION: Patients with early-stage and locally advanced rectal cancer are often treated with neoadjuvant therapy followed by surgery or watch and wait. This study evaluated the role of circulating tumor DNA (ctDNA) to measure disease after neoadjuvant treatment and surgery to optimize treatment choices. MATERIALS AND METHODS: Patients with rectal cancer treated with both chemotherapy and radiotherapy were included and diagnostic biopsies were analyzed for tumor-specific mutations. Presence of ctDNA was measured in plasma by tracing the tumor-informed mutations using a next-generation sequencing panel. The association between ctDNA detection and clinicopathological characteristics and progression-free survival was measured. RESULTS: Before treatment ctDNA was detected in 69% (35/51) of patients. After neoadjuvant therapy ctDNA was detected in only 15% (5/34) of patients. In none of the patients with a complete clinical response who were selected for a watch and wait strategy (0/10) or patients with ypN0 disease (0/8) ctDNA was detected, whereas it was detected in 31% (5/16) of patients with ypN + disease. After surgery ctDNA was detected in 16% (3/19) of patients, of which all (3/3) developed recurrent disease compared to only 13% (2/16) in patients with undetected ctDNA after surgery. In an exploratory survival analysis, both ctDNA detection after neoadjuvant therapy and after surgery was associated with worse progression-free survival (p = 0.01 and p = 0.007, respectively, Cox-regression). CONCLUSION: These data show that in patients with early-stage and locally advanced rectal cancer tumor-informed ctDNA detection in plasma using ultradeep sequencing may have clinical value to complement response prediction after neoadjuvant therapy and surgery.

Circulating Tumor DNA-Based Disease Monitoring of Patients with Locally Advanced Esophageal Cancer.

Patients diagnosed with locally advanced esophageal cancer are often treated with neoadjuvant chemoradiotherapy followed by surgery. This study explored whether detection of circulating tumor DNA (ctDNA) in plasma can be used to predict residual disease during treatment. Diagnostic tissue biopsies from patients with esophageal cancer receiving neoadjuvant chemoradiotherapy and surgery were analyzed for tumor-specific mutations. These tumor-informed mutations were used to measure the presence of ctDNA in serially collected plasma samples using hybrid capture-based sequencing. Plasma samples were obtained before chemoradiotherapy, and prior to surgery. The association between ctDNA detection and progression-free and overall survival was measured. Before chemoradiotherapy, ctDNA was detected in 56% (44/78) of patients and detection was associated with tumor stage and volume (p = 0.05, Fisher exact and p = 0.02, Mann-Whitney, respectively). After chemoradiotherapy, ctDNA was detected in 10% (8/78) of patients. This preoperative detection of ctDNA was independently associated with recurrent disease (hazard ratio 2.8, 95% confidence interval 1.1-6.8, p = 0.03, multivariable Cox-regression) and worse overall survival (hazard ratio 2.9, 95% confidence interval 1.2-7.1, p = 0.02, multivariable Cox-regression).Ultradeep sequencing-based detection of ctDNA in preoperative plasma of patients with locally advanced esophageal cancer may help to assess which patients have a high risk of recurrence after neoadjuvant chemoradiotherapy and surgery.

Shrinkage versus fragmentation response in neoadjuvantly treated oesophageal adenocarcinoma: significant prognostic relevance.

AIMS: No consensus exists on the clinical value of tumour regression grading (TRG) systems for therapy effects of neoadjuvant chemoradiotherapy (nCRT) in oesophageal adenocarcinoma. Existing TRG systems lack standardization and reproducibility, and do not consider the morphological heterogeneity of tumour response. Therefore, we aim to identify morphological tumour regression patterns of oesophageal adenocarcinoma after nCRT and their association with survival. METHODS AND RESULTS: Patients with oesophageal adenocarcinoma, who underwent nCRT followed by surgery and achieved a partial response to nCRT, were identified from two Dutch upper-gastrointestinal (GI) centres (2005-18; test cohort). Resection specimens were scored for regression patterns by two independent observers according to a pre-defined three-step flowchart. The results were validated in an external cohort (2001-17). In total, 110 patients were included in the test cohort and 115 in the validation cohort. In the test cohort, two major regression patterns were identified: fragmentation (60%) and shrinkage (40%), with an excellent interobserver agreement (κ = 0.87). Here, patients with a fragmented pattern had a significantly higher pathological stage (stages III/IV: 52 versus 16%; P < 0.001), less downstaging (48 versus 91%; P < 0.001), a higher risk of recurrence [risk ratio (RR) = 2.9, 95% confidence interval (CI) = 1.5-5.6] and poorer 5-year overall survival (30 versus 80% respectively, P = 0.001). CONCLUSIONS: The validation cohort confirmed these findings, although had more advanced cases (case-stages = III/IV 91 versus 73%, P = 0.005) and a higher prevalence of fragmented-pattern cases (80 versus 60%, P = 0.002). When combining the cohorts in multivariate analysis, the pattern of response was an independent prognostic factor [hazard ratio (HR) = 1.76, 95% CI = 1.0-3.0]. In conclusion, we established an externally validated, reproducible and clinically relevant classification of tumour response.

Recurrent Endometrial Cancer: Local and Systemic Treatment Options.

The treatment of recurrent endometrial cancer is a challenge. Because of earlier treatments and the site of locoregional recurrence, in the vaginal vault or pelvis, morbidity can be high. A total of about 4 to 20% of the patients with endometrial cancer develop a locoregional recurrence, mostly among patients with locally advanced disease. The treatment options are dependent on previous treatments and the site of recurrence. Local and locoregional recurrences can be treated curatively with surgery or (chemo)radiotherapy with acceptable toxicity and control rates. Distant recurrences can be treated with palliative systemic therapy, i.e., first-line chemotherapy or hormonal therapy. Based on the tumor characteristics and molecular profile, there can be a role for immunotherapy. The evidence on targeted therapy is limited, with no approved treatment in the current guidelines. In selected cases, there might be an indication for local treatment in oligometastatic disease. Because of the novel techniques in radiotherapy, disease control can often be achieved at limited toxicity. Further studies are warranted to analyze the survival outcome and toxicity of newer treatment strategies. Patient selection is very important in deciding which treatment is of most benefit, and better prediction models based on the patient- and tumor characteristics are necessary.

Mesorectal shape variation in rectal cancer radiotherapy in prone position using a belly board.

BACKGROUND AND PURPOSE: In rectal cancer patients, radiotherapy in prone position using a belly board can reduce the dose to organs at risk. For this patient group we investigated inter-fraction shape variation of the mesorectal part of the clinical target volume (CTV) and determined planning target volume (PTV) margins. MATERIALS AND METHODS: Patients with rectal cancer receiving neoadjuvant (chemo)radiotherapy were eligible. For each patient a planning computed tomography (pCT) and five cone-beam CT (CBCT) scans were acquired in prone position using a belly board. The mesorectal CTV was delineated on all scans. Mesorectal shape variation was quantified relative to the pCT. PTV margins were derived locally and averaged for separate subregions of the mesorectal CTV. For each patient a total PTV was constructed using our clinical margins for mesorectal and lymph node CTVs. An artificial dose distribution conforming to this PTV was used to calculate the coverage for the mesorectal CTV using the CBCT delineations. RESULTS: In 19 rectal cancer patients the derived PTV margins were smallest in the upper-lateral region (6 mm) and largest in the upper-anterior region (16 mm). PTV margins for the upper-anterior region were larger for female patients (19 mm) compared to male patients (14 mm). Clinical margins for the total PTV were sufficient for a coverage of at least 97% of the mesorectal CTV for all patients. CONCLUSIONS: Mesorectal shape variation is heterogeneous and largest in the upper-anterior region, in rectal cancer patients irradiated in prone position and using a belly board.

Conversion of a colorectal cancer guideline into clinical decision trees with assessment of validity.

OBJECTIVE: The interpretation and clinical application of guidelines can be challenging and time-consuming, which may result in noncompliance to guidelines. The aim of this study was to convert the Dutch guideline for colorectal cancer (CRC) into decision trees and subsequently implement decision trees in an online decision support environment to facilitate guideline application. METHODS: The recommendations of the Dutch CRC guidelines (published in 2014) were translated into decision trees consisting of decision nodes, branches and leaves that represent data items, data item values and recommendations, respectively. Decision trees were discussed with experts in the field and published as interactive open access decision support software (available at www.oncoguide.nl). Decision tree validation and a concordance analysis were performed using consecutive reports (January 2016-January 2017) from CRC multidisciplinary tumour boards (MTBs) at Amsterdam University Medical Centers, location AMC. RESULTS: In total, we developed 34 decision trees driven by 101 decision nodes based on the guideline recommendations. Decision trees represented recommendations for diagnostics (n = 1), staging (n = 10), primary treatment (colon: n = 1, rectum: n = 5, colorectal: n = 9), pathology (n = 4) and follow-up (n = 3) and included one overview decision tree for optimal navigation. We identified several guideline information gaps and areas of inconclusive evidence. A total of 158 patients' MTB reports were eligible for decision tree validation and resulted in treatment recommendations in 80% of cases. The concordance rate between decision tree treatment recommendations and MTB advices was 81%. Decision trees reported in 22 out of 24 non-concordant cases (92%) that no guideline recommendation was available. CONCLUSIONS: We successfully converted the Dutch CRC guideline into decision trees and identified several information gaps and areas of inconclusive evidence, the latter being the main cause of the observed disagreement between decision tree recommendations and MTB advices. Decision trees may contribute to future strategies to optimize quality of care for CRC patients.

Radiotherapy quality assurance for mesorectum treatment planning within the multi-center phase II STAR-TReC trial: Dutch results.

BACKGROUND: The STAR-TReC trial is an international multi-center, randomized, phase II study assessing the feasibility of short-course radiotherapy or long-course chemoradiotherapy as an alternative to total mesorectal excision surgery. A new target volume is used for both (chemo)radiotherapy arms which includes only the mesorectum. The treatment planning QA revealed substantial variation in dose to organs at risk (OAR) between centers. Therefore, the aim of this study was to determine the treatment plan variability in terms of dose to OAR and assess the effect of a national study group meeting on the quality and variability of treatment plans for mesorectum-only planning for rectal cancer. METHODS: Eight centers produced 25 × 2 Gy treatment plans for five cases. The OAR were the bowel cavity, bladder and femoral heads. A study group meeting for the participating centers was organized to discuss the planning results. At the meeting, the values of the treatment plan DVH parameters were distributed among centers so that results could be compared. Subsequently, the centers were invited to perform replanning if they considered this to be necessary. RESULTS: All treatment plans, both initial planning and replanning, fulfilled the target constraints. Dose to OAR varied considerably for the initial planning, especially for dose levels below 20 Gy, indicating that there was room for trade-offs between the defined OAR. Five centers performed replanning for all cases. One center did not perform replanning at all and two centers performed replanning on two and three cases, respectively. On average, replanning reduced the bowel cavity V20Gy by 12.6%, bowel cavity V10Gy by 22.0%, bladder V35Gy by 14.7% and bladder V10Gy by 10.8%. In 26/30 replanned cases the V10Gy of both the bowel cavity and bladder was lower, indicating an overall lower dose to these OAR instead of a different trade-off. In addition, the bowel cavity V10Gy and V20Gy showed more similarity between centers. CONCLUSIONS: Dose to OAR varied considerably between centers, especially for dose levels below 20 Gy. The study group meeting and the distribution of the initial planning results among centers resulted in lower dose to the defined OAR and reduced variability between centers after replanning. TRIAL REGISTRATION: The STAR-TReC trial, ClinicalTrials.gov Identifier: NCT02945566. Registered 26 October 2016, https://clinicaltrials.gov/ct2/show/NCT02945566).

Low-Dose Versus High-Dose Radiation Therapy for the Palliation of Dysphagia From Esophageal Cancer: A Multicenter Retrospective Cohort Study.

PURPOSE: Clinical evidence regarding optimal radiation dose for palliation of dysphagia from esophageal cancer is generally lacking. In an effort to investigate optimal radiation dose, we assessed 2 different radiation schedules for palliation of dysphagia. METHODS AND MATERIALS: We performed a multicenter, retrospective study comparing low-dose radiation therapy (LR: 5 x 4 Gy external beam radiation therapy [EBRT]) with high-dose radiation therapy (HR: 10 x 3 Gy EBRT and 12-Gy single-dose intraluminal brachytherapy) for palliation of dysphagia in patients with inoperable or metastasized esophageal cancer. Primary outcome was improvement of dysphagia at 6 weeks after start of radiation therapy. Additional outcomes were persistent and recurrent dysphagia during patients' remaining life, severe adverse events, and survival. RESULTS: In total, 292 patients (LR, n = 117; HR, n = 175) were included in this study. After matching, 144 patients (72 in each group) were compared. Improvement of dysphagia at 6 weeks was achieved in 50% of patients after LR and in 66% after HR (P = .071). Persistent or recurrent dysphagia occurred in 64% of patients after LR and in 42% after HR (P = .012). No difference in the rate of severe adverse events was found (P = .889). Median survival was 88 days (95% confidence interval, 64-112) after LR and 177 days (95% confidence interval, 131-223) after HR (P < .001). CONCLUSIONS: This study shows that both LR and HR were well tolerated and effective in short-term relief of dysphagia in patients with inoperable or metastasized esophageal cancer. HR was associated with better long-term relief of dysphagia compared with LR. Our findings suggest that HR could be considered for patients with a longer life expectancy, but prospective studies are required.

Addition of MRI for CT-based pancreatic tumor delineation: a feasibility study.

PURPOSE: To assess the effect of additional magnetic resonance imaging (MRI) alongside the planning computed tomography (CT) scan on target volume delineation in pancreatic cancer patients. MATERIAL AND METHODS: Eight observers (radiation oncologists) from six institutions delineated the gross tumor volume (GTV) on 3DCT, and internal GTV (iGTV) on 4DCT of four pancreatic cancer patients, while MRI was available in a second window (CT + MRI). Variations in volume, generalized conformity index (CIgen), and overall observer variation, expressed as standard deviation (SD) of the distances between delineated surfaces, were analyzed. CIgen is a measure of overlap of the delineated iGTVs (1 = full overlap, 0 = no overlap). Results were compared with those from an earlier study that assessed the interobserver variation by the same observers on the same patients on CT without MRI (CT-only). RESULTS: The maximum ratios between delineated volumes within a patient were 6.1 and 22.4 for the GTV (3DCT) and iGTV (4DCT), respectively. The average (root-mean-square) overall observer variations were SD = 0.41 cm (GTV) and SD = 0.73 cm (iGTV). The mean CIgen was 0.36 for GTV and 0.37 for iGTV. When compared to the iGTV delineated on CT-only, the mean volumes of the iGTV on CT + MRI were significantly smaller (32%, Wilcoxon signed-rank, p < .0005). The median volumes of the iGTV on CT + MRI were included for 97% and 92% in the median volumes of the iGTV on CT. Furthermore, CT + MRI showed smaller overall observer variations (root-mean-square SD = 0.59 cm) in six out of eight delineated structures compared to CT-only (root-mean-square SD = 0.72 cm). However, large local observer variations remained close to biliary stents and pathological lymph nodes, indicating issues with instructions and instruction compliance. CONCLUSIONS: The availability of MRI images during target delineation of pancreatic cancer on 3DCT and 4DCT resulted in smaller target volumes and reduced the interobserver variation in six out of eight delineated structures.

Outcome and prognostic factors in 110 consecutive patients with primary uterine leiomyosarcoma: A Rare Cancer Network study.

OBJECTIVE: Primary uterine leiomyosarcomas (ULMS) are rare, and the optimal treatment is controversial. We aimed to assess the outcome and prognostic factors in a multicenter population of women treated for primary ULMS. METHODS: We retrospectively collected data of 110 women treated in 19 institutions of the Rare Cancer Network (RCN). Inclusion criteria consisted of a pathology report confirming the diagnosis of ULMS, aged 18-80 years, complete International Federation of Gynecology and Obstetrics (FIGO) stage information, complete information on treatment, and a minimum follow-up of 6 months. Local control (LC) and locoregional control (LRC), overall survival (OS) and disease-free survival (DFS) rates were computed using the Kaplan-Meier method. Univariate analysis was implemented using the log rank test, and multivariate analysis using the Cox model. RESULTS: All patients underwent surgery. Seventy-five patients (68%) received adjuvant radiotherapy (RT), including brachytherapy in 18 (16%). Seventeen patients (15%) received adjuvant chemotherapy. Median follow-up was 58 (range, 6-240) months. Five-year OS and DFS rates were 50% and 34%, and LC and LRC rates were 88% and 72%, respectively. On multivariate analysis, independent favorable prognostic factors were younger age, FIGO stage I, small tumor size, previous uterine disease, and no vascular invasion for OS and DFS. FIGO stage was the only favorable factor influencing LRC. Adjuvant local or systemic treatments did not improve the outcomes. Eight patients treated with RT presented a grade 3 acute toxicity, and only one patient with grade 3 late toxicity. CONCLUSIONS: In this large population of primary ULMS patients, we found good results in terms of LC and LRC. Nevertheless, OS remains poor, mainly due to the occurrence of distant metastases. An early diagnosis seemed to improve the prognosis of the patients. Adjuvant local or systemic treatments, or more aggressive surgical procedures such as the Wertheim procedure, did not seem to impact the outcome.

Treatment of Locally Recurrent Rectal Carcinoma in Previously (Chemo)Irradiated Patients: A Review.

BACKGROUND: Local recurrence after rectal cancer treatment occurs in ≈5% to 10% of patients. Neoadjuvant (chemo)radiotherapy for primary rectal cancer renders treatment of recurrent disease more difficult. OBJECTIVE: The purpose of this study was to review contemporary multimodality therapies, including their outcome, for locally recurrent rectal carcinoma after (chemo)radiotherapy and complete surgical resection of primary rectal cancer. DATA SOURCES: A comprehensive literature search of PubMed and EMBASE was performed. STUDY SELECTION: All English language articles presenting original patient data regarding treatment and the respective outcome of previously irradiated locally recurrent rectal cancer were included. INTERVENTIONS: All of the treatment modalities for locally recurrent rectal cancer were reviewed. MAIN OUTCOME MEASURES: Primary outcome parameters were local control, metastasis-free survival, and overall survival. Secondary outcome parameters were perioperative morbidity and mortality, and prognostic factors for treatment outcome. RESULTS: Of 854 studies, 9 studies and 474 patients with locally recurrent rectal carcinoma were included. Various treatment regimens were used, most with curative intent. Reirradiation was composed of (neo-)adjuvant external beam radiotherapy (with or without concurrent chemotherapy), additional intraoperative radiotherapy, or intraoperative radiotherapy only. Surgical technique highly varied, depending on the extent of the lesion. Radiation toxicity, perioperative morbidity, and mortality were generally acceptable. Outcome was better after curative intent treatment, any surgical resection, and R0 resections in particular. Moreover, reirradiation is associated with increased complete resection rates, which in turn positively affected local control and overall survival. LIMITATIONS: Most studies were retrospectively designed, with highly variable therapies, patient populations, and duration of follow-up. CONCLUSIONS: A complete resection is the most important prognostic factor and should be the goal of treatment in locally recurrent rectal carcinoma. Reirradiation seems safe and of additional value in reaching a complete resection. Considering the available evidence, at present reirradiation should be given on a case-specific basis, with all of the patients entering an international prospective database.

Patterns of recurrence after surgery alone versus preoperative chemoradiotherapy and surgery in the CROSS trials.

PURPOSE: To analyze recurrence patterns in patients with cancer of the esophagus or gastroesophageal junction treated with either preoperative chemoradiotherapy (CRT) plus surgery or surgery alone. PATIENTS AND METHODS: Recurrence pattern was analyzed in patients from the previously published CROSS I and II trials in relation to radiation target volumes. CRT consisted of five weekly courses of paclitaxel and carboplatin combined with a concurrent radiation dose of 41.4 Gy in 1.8-Gy fractions to the tumor and pathologic lymph nodes with margin. RESULTS: Of the 422 patients included from 2001 to 2008, 418 were available for analysis. Histology was mostly adenocarcinoma (75%). Of the 374 patients who underwent resection, 86% were allocated to surgery and 92% to CRT plus surgery. On January 1, 2011, after a minimum follow-up of 24 months (median, 45 months), the overall recurrence rate in the surgery arm was 58% versus 35% in the CRT plus surgery arm. Preoperative CRT reduced locoregional recurrence (LRR) from 34% to 14% (P < .001) and peritoneal carcinomatosis from 14% to 4% (P < .001). There was a small but significant effect on hematogenous dissemination in favor of the CRT group (35% v 29%; P = .025). LRR occurred in 5% within the target volume, in 2% in the margins, and in 6% outside the radiation target volume. In 1%, the exact site in relation to the target volume was unclear. Only 1% had an isolated infield recurrence after CRT plus surgery. CONCLUSION: Preoperative CRT in patients with esophageal cancer reduced LRR and peritoneal carcinomatosis. Recurrence within the radiation target volume occurred in only 5%, mostly combined with outfield failures.

Nutritional status, food intake, and dysphagia in long-term survivors with head and neck cancer treated with chemoradiotherapy: a cross-sectional study.

BACKGROUND: The aim of this study was to evaluate nutritional status, food intake, and dysphagia in long-term head and neck cancer survivors. METHODS: Thirty-two patients with stage III-IV head and neck cancer treated by chemoradiotherapy were invited to evaluate nutritional status (malnutrition, relative weight loss), food intake (food modification; quality), and dysphagia. RESULTS: At a median follow up of 44 months, 6 of 32 patients were at risk for malnutrition. Women (p = .049) and patients with high body mass index before treatment (p = .024) showed more weight loss. None of the 32 patients could eat a "full diet." Six patients used nutritional supplements/tube feeding. Low dysphagia-related quality of life scores were significantly correlated to increased food modification (r = 0.405; p = .024). CONCLUSIONS: Nutritional advice in patients with head and neck cancer is still necessary years after chemoradiation and should focus on nutritional status, food modification, and quality, in accord with recommended food groups.

The CARTS study: Chemoradiation therapy for rectal cancer in the distal rectum followed by organ-sparing transanal endoscopic microsurgery.

BACKGROUND: The CARTS study is a multicenter feasibility study, investigating the role of rectum saving surgery for distal rectal cancer. METHODS/DESIGN: Patients with a clinical T1-3 N0 M0 rectal adenocarcinoma below 10 cm from the anal verge will receive neoadjuvant chemoradiation therapy (25 fractions of 2 Gy with concurrent capecitabine). Transanal Endoscopic Microsurgery (TEM) will be performed 8 - 10 weeks after the end of the preoperative treatment depending on the clinical response.Primary objective is to determine the number of patients with a (near) complete pathological response after chemoradiation therapy and TEM. Secondary objectives are the local recurrence rate and quality of life after this combined therapeutic modality. A three-step analysis will be performed after 20, 33 and 55 patients to ensure the feasibility of this treatment protocol. DISCUSSION: The CARTS-study is one of the first prospective multicentre trials to investigate the role of a rectum saving treatment modality using chemoradiation therapy and local excision. The CARTS study is registered at clinicaltrials.gov (NCT01273051).

Long-term outcome and morbidity after treatment with accelerated radiotherapy and weekly cisplatin for locally advanced head-and-neck cancer: results of a multidisciplinary late morbidity clinic.

PURPOSE: To evaluate the long-term outcome and morbidity after intensified treatment for locally advanced head-and-neck cancer. METHODS AND MATERIALS: Between May 2003 and December 2007, 77 patients with Stage III to IV head-and-neck cancer were treated with curative intent. Treatment consisted of accelerated radiotherapy to a dose of 68 Gy and concurrent cisplatin. Long-term survivors were invited to a multidisciplinary outpatient clinic for a comprehensive assessment of late morbidity with special emphasis on dysphagia, including radiological evaluation of swallowing function in all patients. RESULTS: Compliance with the treatment protocol was high, with 87% of the patients receiving at least five cycles of cisplatin and all but 1 patient completing the radiotherapy as planned. The 5-year actuarial disease-free survival and overall survival rates were 40% and 47%, respectively. Locoregional recurrence-free survival at 5 years was 61%. The 5-year actuarial rates of overall late Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) Grade 3 and Grade 4 toxicity were 52% and 25% respectively. Radiologic evaluation after a median follow-up of 44 months demonstrated impaired swallowing in 57% of the patients, including 23% with silent aspiration. Subjective assessment using a systematic scoring system indicated normalcy of diet in only 15.6% of the patients. CONCLUSION: This regimen of accelerated radiotherapy with weekly cisplatin produced favorable tumor control rates and survival rates while compliance was high. However, comprehensive assessment by a multidisciplinary team of medical and paramedical specialists revealed significant long-term morbidity in the majority of the patients, with dysphagia being a major concern.