Adjuvant Therapy for Patients with a Tumor-Positive Resection Margin After Neoadjuvant Chemoradiotherapy and Esophagectomy.

BACKGROUND: Approximately 4-9% of patients have a tumor-positive resection margin after neoadjuvant chemoradiotherapy (nCRT) and esophagectomy. Although it is associated with decreased survival, Western guidelines do not recommend adjuvant treatment. OBJECTIVE: The aim of this study was to assess the proportion of patients who received adjuvant therapy, and to evaluate overall survival (OS) after esophagectomy in patients with a tumor-positive resection margin. METHODS: Patients diagnosed with resectable (cT2-4a/cTxN0-3/NxM0) esophageal cancer between 2015 and 2022, and treated with nCRT followed by irradical esophagectomy, were selected from the Netherlands Cancer Registry. The primary outcome was the proportion of patients with a tumor-positive resection margin who started adjuvant treatment ≤16 weeks after esophagectomy, including chemotherapy/radiotherapy, immunotherapy, or targeted therapy. OS was calculated from the date of surgery until the date of death or last day of follow-up. RESULTS: Overall, 376 patients were included in our study, of whom 357 were treated with nCRT. Of these 357 patients, 98.3% had a microscopically irradical resection and 1.7% had a macroscopically irradical resection. Approximately 72.3% of tumors showed a partial response (Mandard 2-3) and 11.8% showed little/no pathological response (Mandard 4-5) to nCRT. One of 357 patients underwent adjuvant chemoradiotherapy and 39 patients (61%) underwent adjuvant immunotherapy (nivolumab). The median and 5-year OS rate of all patients was 16.4 months (95% confidence interval 13.1-19.8) and 21%, respectively. CONCLUSION: Real-world population-level data showed that no patients with a tumor-positive resection margin underwent adjuvant therapy following nCRT and esophagectomy prior to 2021. Interestingly, 61% of patients were treated with adjuvant nivolumab in 2021-2022. OS after irradical esophagectomy is poor and long-term data will explore the added value of nivolumab.

Stereotactic ablative radiotherapy or best supportive care in patients with localized pancreatic cancer not receiving chemotherapy and surgery (PANCOSAR): a nationwide multicenter randomized controlled trial according to a TwiCs design.

BACKGROUND: Significant comorbidities, advanced age, and a poor performance status prevent surgery and systemic treatment for many patients with localized (non-metastatic) pancreatic ductal adenocarcinoma (PDAC). These patients are currently treated with 'best supportive care'. Therefore, it is desirable to find a treatment option which could improve both disease control and quality of life in these patients. A brief course of high-dose high-precision radiotherapy i.e. stereotactic ablative body radiotherapy (SABR) may be feasible. METHODS: A nationwide multicenter trial performed within a previously established large prospective cohort (the Dutch Pancreatic cancer project; PACAP) according to the 'Trial within cohorts' (TwiCs) design. Patients enrolled in the PACAP cohort routinely provide informed consent to answer quality of life questionnaires and to be randomized according to the TwiCs design when eligible for a study. Patients with localized PDAC who are unfit for chemotherapy and surgery or those who refrain from these treatments are eligible. Patients will be randomized between SABR (5 fractions of 8 Gy) with 'best supportive care' and 'best supportive care' only. The primary endpoint is overall survival from randomization. Secondary endpoints include preservation of quality of life (EORTC-QLQ-C30 and -PAN26), NRS pain score response and WHO performance scores at baseline, and, 3, 6 and 12 months. Acute and late toxicity will be scored using CTCAE criteria version 5.0: assessed at baseline, day of last fraction, at 3 and 6 weeks, and 3, 6 and 12 months following SABR. DISCUSSION: The PANCOSAR trial studies the added value of SBRT as compared to 'best supportive care' in patients with localized PDAC who are medically unfit to receive chemotherapy and surgery, or refrain from these treatments. This study will assess whether SABR, in comparison to best supportive care, can relieve or delay tumor-related symptoms, enhance quality of life, and extend survival in these patients. TRIAL REGISTRATION: Clinical trials, NCT05265663 , Registered March 3 2022, Retrospectively registered.

Relation between body composition and severe diarrhea in patients treated with preoperative chemoradiation with capecitabine for rectal cancer: a single-centre cohort study.

BACKGROUND: Chemoradiation with capecitabine followed by surgery is standard care for locally advanced rectal cancer (LARC). Severe diarrhea is considered a dose-limiting toxicity of adding capecitabine to radiation therapy. The aim of this study was to describe the risk factors and the impact of body composition on severe diarrhea in patients with LARC during preoperative chemoradiation with capecitabine. METHODS: A single centre retrospective cohort study was conducted in a tertiary referral centre. All patients treated with preoperative chemoradiation with capecitabine for LARC from 2009 to 2015 were included. Patients with locally recurrent rectal cancer who received chemoradiation for the first time were included as well. Logistic regression analyses were performed to identify risk factors for severe diarrhea. RESULTS: A total of 746 patients were included. Median age was 64 years (interquartile range 57-71) and 477 patients (64%) were male. All patients received a radiation dosage of 25 × 2 Gy during a period of five weeks with either concomitant capecitabine administered on radiation days or continuously during radiotherapy. In this cohort 70 patients (9%) developed severe diarrhea. In multivariable logistic regression analyses female sex (OR: 4.42, 95% CI 2.54-7.91) and age ≥ 65 (OR: 3.25, 95% CI 1.85-5.87) were the only risk factors for severe diarrhea. CONCLUSIONS: Female patients and patients aged sixty-five or older had an increased risk of developing severe diarrhea during preoperative chemoradiation therapy with capecitabine. No relation was found between body composition and severe diarrhea.

Treatment of Inguinal Lymph Node Metastases in Patients with Rectal Adenocarcinoma.

BACKGROUND: Inguinal lymph node metastases (ILNM) from rectal adenocarcinoma are rare and staged as systemic disease. This study aimed to provide insight into the treatment and prognosis of ILNM from rectal adenocarcinoma. METHODS: All patients with a diagnosis of synchronous or metachronous ILNM from rectal adenocarcinoma between January 2005 and March 2017 were retrospectively reviewed. RESULTS: The study identified 27 patients with ILNM (15 with synchronous and 12 with metachronous disease). After discussion by a multidisciplinary tumor board, 19 patients were treated with curative intent, 17 of whom underwent inguinal lymph node dissection. Of the 17 patients, 12 had locally advanced rectal cancer (LARC) with isolated ILNM, 3 had LARC and metastases elsewhere, and 2 had locally recurrent rectal cancer (LRRC). The median overall survival (OS) for all the patients treated with curative intent was 27 months [95% confidence interval (CI) 11.6-42.4 months], with a 5-year OS rate of 34%. The median OS for the patients with LARC and isolated ILNM (n = 12) was 74 months (95% CI 18.0-130.0 months), with a 5-year OS rate of 52%. All the patients with metastases elsewhere (n = 3) or LRRC (n = 2) experienced recurrent systemic disease. Eight patients were treated with palliative intent. The median OS for this group was 13 months (95% CI 1.9-24.1 months), with a 3-year OS rate of 0%. CONCLUSION: Clinicians should not consider ILNM as an incurable systemic disease. Patients with primary rectal cancer and solitary ILNM who were eligible for curative surgical treatment had a 5-year survival rate of 52%. The prognosis for patients with additional systemic metastases or LRRC is worse, and the benefit of surgery is unclear.

Salvage Abdominoperineal Resection for Squamous Cell Anal Cancer: A 30-Year Single-Institution Experience.

BACKGROUND: Failure of chemoradiotherapy (CRT) for anal squamous cell carcinoma (SCC) results in persistent or recurrent anal SCC. Treatment with salvage abdominoperineal resection (APR) can potentially achieve cure. The aims of this study are to analyze oncological and surgical outcomes of our 30-year experience with salvage APR for anal SCC after failed CRT and identify prognostic factors for overall survival (OS). METHODS: All consecutive patients who underwent salvage APR between 1990 and 2016 for histologically confirmed persistent or recurrent anal SCC after failed CRT were retrospectively analyzed. RESULTS: Forty-seven patients underwent salvage APR for either persistent (n = 24) or recurrent SCC (n = 23). Median OS was 47 months [95% confidence interval (CI) 10.0-84.0 months] and 5-year survival was 41.6%, which did not differ significantly between persistent or recurrent disease (p = 0.551). Increased pathological tumor size (p < 0.001) and lymph node involvement (p = 0.014) were associated with impaired hazard for OS on multivariable analysis, and irradical resection only (p = 0.001) on univariable analysis. Twenty-one patients developed local recurrence after salvage APR, of whom 8 underwent repeat salvage surgery and 13 received palliative treatment. Median OS was 9 months (95% CI 7.2-10.8 months) after repeat salvage surgery and 4 months (95% CI 2.8-5.1 months) following palliative treatment (p = 0.055). CONCLUSIONS: Salvage APR for anal SCC after failed CRT resulted in adequate survival, with 5-year survival of 41.6%. Negative prognostic factors for survival were increased tumor size, lymph node involvement, and irradical resection. Patients with recurrent anal SCC after salvage APR had poor prognosis, irrespective of performance of repeat salvage surgery, which never resulted in cure.

Treatment selection of early stage non-small cell lung cancer: the role of the patient in clinical decision making.

BACKGROUND: The objective of this study is to investigate the role and experience of early stage non-small cell lung cancer (NSCLC) patient in decision making process concerning treatment selection in the current clinical practice. METHODS: Stage I-II NSCLC patients (surgery 55 patients, SBRT 29 patients, median age 68) were included in this prospective study and completed a questionnaire that explored: (1) perceived patient knowledge of the advantages and disadvantages of the treatment options, (2) experience with current clinical decision making, and (3) the information that the patient reported to have received from their treating physician. This was assessed by multiple-choice, 1-5 Likert Scale, and open questions. The Decisional Conflict Scale was used to assess the decisional conflict. Health related quality of life (HRQoL) was measured with SF-36 questionnaire. RESULTS: In 19% of patients, there was self-reported perceived lack of knowledge about the advantages and disadvantages of the treatment options. Seventy-four percent of patients felt that they were sufficiently involved in decision-making by their physician, and 81% found it important to be involved in decision making. Forty percent experienced decisional conflict, and one-in-five patients to such an extent that it made them feel unsure about the decision. Subscores with regard to feeling uninformed and on uncertainty, contributed the most to decisional conflict, as 36% felt uninformed and 17% of patients were not satisfied with their decision. HRQoL was not influenced by patient experience with decision-making or patient preferences for shared decision making. CONCLUSIONS: Dutch early-stage NSCLC patients find it important to be involved in treatment decision making. Yet a substantial proportion experiences decisional conflict and feels uninformed. Better patient information and/or involvement in treatment-decision-making is needed in order to improve patient knowledge and hopefully reduce decisional conflict.

Meta-analysis of the influence of surgical margin and adjuvant radiotherapy on local recurrence after resection of sporadic desmoid-type fibromatosis.

BACKGROUND: Extra-abdominal desmoid-type fibromatosis (DF) is a rare, locally aggressive neoplasm that is usually managed conservatively. When treatment is indicated, it typically involves surgical resection, possibly with adjuvant radiotherapy. The indications for postoperative radiotherapy and its effectiveness are unclear. The objective of this study was to estimate the effect of surgical resection margins and adjuvant radiotherapy on rates of recurrence of DF. METHODS: Literature published between 1999 and 2015 was extracted from MEDLINE, Embase, Cochrane Central Registry of Trials, Web of Science and Google Scholar. Recurrence rate was analysed by meta-analysis and compared between subgroups. RESULTS: Sixteen reports were included, consisting of a total of 1295 patients with DF. In patients treated by surgical resection alone, the risk of local recurrence was almost twofold higher for those with microscopically positive resection margins (risk ratio (RR) 1·78, 95 per cent c.i. 1·40 to 2·26). Adjuvant radiotherapy after surgery with negative margins had no detectable benefit on recurrence. In contrast, after incomplete surgical resection, adjuvant radiotherapy improved recurrence rates both in patients with primary tumours (RR 1·54, 1·05 to 2·27) and in those with recurrent DF (RR 1·60, 1·12 to 2·28). CONCLUSION: DF resected with microscopically positive margins has a higher risk of recurrence. Adjuvant radiotherapy appears to reduce the risk of recurrence after incomplete surgical resection, particularly in patients with recurrent tumours.

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

BACKGROUND: This prospective multicentre study was performed to quantify the number of patients with minimal residual disease (ypT0-1) after neoadjuvant chemoradiotherapy and transanal endoscopic microsurgery (TEM) for rectal cancer. METHODS: Patients with clinically staged T1-3 N0 distal rectal cancer were treated with long-course chemoradiotherapy. Clinical response was evaluated 6-8 weeks later and TEM performed. Total mesorectal excision was advocated in patients with residual disease (ypT2 or more). RESULTS: The clinical stage was cT1 N0 in ten patients, cT2 N0 in 29 and cT3 N0 in 16 patients. Chemoradiotherapy-related complications of at least grade 3 occurred in 23 of 55 patients, with two deaths from toxicity, and two patients did not have TEM or major surgery. Among 47 patients who had TEM, ypT0-1 disease was found in 30, ypT0 N1 in one, ypT2 in 15 and ypT3 in one. Local recurrence developed in three of the nine patients with ypT2 tumours who declined further surgery. Postoperative complications grade I-IIIb occurred in 13 of 47 patients after TEM and in five of 12 after (completion) surgery. After a median follow-up of 17 months, four local recurrences had developed overall, three in patients with ypT2 and one with ypT1 disease. CONCLUSION: TEM after chemoradiotherapy enabled organ preservation in one-half of the patients with rectal cancer.

Response to chemotherapy in patients with recurrent rectal cancer in previously irradiated area.

BACKGROUND: Tumor lesions in previously irradiated area may have a less favorable response to chemotherapy compared to tumor sites outside the radiation field. The aim of the present study was to evaluate the response to chemotherapy of locally recurrent rectal cancer (LRRC) within the previous radiation field compared to the response of distant metastases outside the radiation field. PATIENTS AND METHODS: All patients with LRRC referred between 2000 and 2012 to our tertiary university hospital were reviewed. The response to chemotherapy of LRRC within previously irradiated area was compared to the response of synchronous distant metastases outside the radiation field according to the Response Evaluation Criteria in Solid Tumors (RECIST). RESULTS: Out of 363 cases with LRRC, 29 previously irradiated patients with distant metastases were treated with chemotherapy and eligible for analysis. Twenty-six patients (89 %) suffered a first recurrence and three patients (11 %) a second recurrence. These patients were followed with a median of 22 months (IQR, 9-40 months) and had a median survival of 33 months (IQR, 14-42). In 23 patients (79 %), the local recurrence showed stable disease, but the overall response rate of the local recurrences in the previously irradiated area was significantly lower than the response rate of distant metastases outside the radiation field (10 vs. 41 %,p = 0.034). CONCLUSIONS: Previously irradiated patients with LRRC have a lower response rate to chemotherapy of the local recurrence within the radiation field compared to the response rate of distant metastases outside the radiation field. This suggests that chemotherapy for local palliation may not have the desired effect.

Palliative radiotherapy: New prognostic factors for patients with bone metastasis.

PURPOSE: Many cancer patients develop bone metastases, however the prognosis of overall survival differs. To provide an optimal treatment for these patients, especially towards the end of life, a reliable prediction of survival is needed. The goal of this study was to find new clinical factors in relation to overall survival. MATERIALS AND METHODS: Prospectively 22 clinical factors were collected from 734 patients. The Kaplan-Meier and Cox regression models were used. RESULTS: Most patients were diagnosed with lung cancer (29%), followed by prostate (19.8%) and breast cancer (14.7%). Median overall survival was 6.4months. Fourteen clinical factors showed significance in the univariate analyses. In the multivariate analyses 6 factors were found to be significant for the overall survival: Karnofsky performance status, primary tumor, gender, total organs affected, morphine use and systemic treatment options after radiotherapy. CONCLUSION: Morphine use and systemic treatment options after radiotherapy, Karnofsky performance status, primary tumor, gender and total organs affected are strong prediction factors on overall survival after palliative radiotherapy in patients with bone metastasis. These factors are easily applicable in the clinic.

A phase II study of stereotactic radiotherapy after FOLFIRINOX for locally advanced pancreatic cancer (LAPC-1 trial): Long-term outcome.

PURPOSE: To report the long-term outcome of a multicenter phase II study with FOLFIRINOX followed by stereotactic body radiotherapy (LAPC-1 trial) in patients with locally advanced pancreatic cancer (LAPC). MATERIALS AND METHODS: Patients with histological confirmation of LAPC inoperable at diagnosis were enrolled. Induction therapy with 8 cycles of FOLFIRINOX was administered. If no disease progression was found after chemotherapy, patients received stereotactic body radiotherapy (SBRT) at a total dose of 40 Gy in 5 fractions. RESULTS: In LAPC-1 trial, 50 patients were included, but due to disease progression in 11 patients under chemotherapy, 39 patients received stereotactic SBRT after FOLFIRINOX treatment. In whole population, the 1- and 3-year overall survival (OS) were 62% and 10%, respectively. Median follow-up was 13 months. The SBRT group had median OS of 18 months (95% CI 13.2-21.5) versus 5 months (95% CI 4.1-6.7) in non-SBRT group (p<0.001). After chemoradiotherapy, seven patients underwent surgery achieving a radical resection. Patients who underwent surgery had a 3-years OS of 43% compared to 6.5% in the unresected group (p=0.03). Four patients developed grade ≥ 3 adverse events during SBRT. CONCLUSIONS: Long-term survival has been found in patients with LAPC underwent FOLFIRINOX followed by SBRT. This approach increased the probability of a radical surgery. The resected patients achieved a significant better survival compared to unresected group.

The clinical relevance of indeterminate lung nodules in patients with locally recurrent rectal cancer.

AIM: To evaluate the clinical relevance of indeterminate lung nodules (ILN) in patients with locally recurrent rectal cancer (LRRC) treated in a tertiary referral centre. METHODS: All patients with LRRC diagnosed between 2000 and 2017 were retrospectively reviewed. Reports of staging chest CT-scans were evaluated for ILN. Patients with distant metastases including lung metastases at time of LRRC diagnosis were excluded. Overall (OS), progression-free survival (PFS) and the cumulative incidence of lung metastases were compared between patients with and without ILN. RESULTS: In total 556 patients with LRRC were treated during the study period. In the 243 patients eligible for analysis, 68 (28%) had ILN at LRRC diagnosis. Median OS was 37 months for both the patients with and without ILN (p = 0.37). Median PFS was 14 months for the patients with ILN and 16 months for patients without ILN (p = 0.80). After correction for potential confounding, ILN present at LRRC diagnosis was not associated with impaired OS or PFS (adjusted hazards ratio [95% confidence interval]: 0.81 [0.54-1.22] and 1.09 [0.75-1.59]). The 5-year cumulative incidence of lung metastases was 31% in patients with ILN and 28% in patients without ILN (p = 0.19). CONCLUSION: Our study shows that ILN are present in roughly a quarter of patients with LRRC. No differences in OS, PFS, or the cumulative incidence of lung metastases were found between patients with and without ILN at LRRC diagnosis. These results suggest that ILN are of little to no clinical relevance in patients with LRRC.

Locally recurrent rectal cancer; long-term outcome of curative surgical and non-surgical treatment of 447 consecutive patients in a tertiary referral centre.

INTRODUCTION: The majority of patients with locally recurrent rectal cancer (LRRC) present with extensive metastatic disease or an unresectable recurrence, and will be treated palliatively. Only a minority of patients will be eligible for potential cure by surgical treatment. The aim of this study is to evaluate the long-term outcome of surgical treatment and non-surgical treatment of patients with LRRC. METHODS: All patients with LRRC referred to our tertiary institute between 2000 and 2015 were retrospectively analysed. Patients were discussed in a multidisciplinary tumour board (MDT) and eventually received curative surgical or non-surgical treatment. Overall survival (OS) was compared by resection margin status and non-surgical treatment. RESULTS: A total of 447 patients were discussed in our MDT of which 193 patients underwent surgical treatment and 254 patients received non-surgical treatment. Surgically treated patients were significantly younger, received less neoadjuvant therapy for the primary tumour, had less metastasis at diagnosis and more central recurrences. The 5-year OS was 51% for R0-resections and 34% for R1-resections. Although numbers with R2-resections were too small to implicate prognostic significance, there was no difference in 5-year OS between R2-resections and non-surgical treatment (10% vs. 4%, p = 0.282). In a subgroup analysis the OS of R2-patients was even poorer compared to optimal palliative treated patients with combined chemotherapy and radiotherapy (22 vs 29 months, p = 0.413). CONCLUSION: R2-resections do not result in a survival benefit compared to non-surgical treatment in this non-randomized series. Patients with a high chance on a R2-resection could be offered non-surgical treatment, without local resection.

The liver-first approach for locally advanced rectal cancer and synchronous liver metastases.

BACKGROUND: Patients with locally advanced rectal cancer (LARC) and synchronous liver metastases (sRLM) can be treated according to the liver-first approach. This study aimed to evaluate prognostic factors for completing treatment and in how many patients extensive lower pelvic surgery might have been omitted. METHODS: Retrospective analysis of all patients with LARC and sRLM treated at the Erasmus MC Cancer Institute according to the liver-first between 2003 and 2016. RESULTS: In total 129 consecutive patients were included. In 90 patients (70%) the liver-first was completed. Ten patients had a (near) complete response (ypT0-1N0) of their primary tumour. In 36 out of 39 patients not completing the liver-first protocol palliative rectum resection was withheld. Optimal cut-offs for CEA level (53.15 µg/L), size (3.85 cm) and number (4) of RLMs were identified. A preoperative CEA level above 53.15 µg/L was an independent predictor for non-completion of the liver-first protocol (p = 0.005). CONCLUSION: Ten patients had a (near) complete response of their primary tumour and, in retrospect, rectum sparing therapies could have been considered. Together with 36 patient in whom palliative rectum resection was not necessary this entails that nearly 40% patients with LARC and sRLM might be spared major pelvic surgery if the liver-first approach is applied. A predictor (CEA) was found for non-completion of the liver-first protocol. The majority of patients underwent resection of both primary tumour and hepatic metastasis with curative intent. These findings together entail that the liver-first approach may be considered in patients with LARC and sRLM.

Postoperative surveillance of pancreatic cancer patients.

BACKGROUND: The aim of this study is to collect the best available evidence for diagnostic modalities, frequency, and duration of surveillance after resection for pancreatic ductal adenocarcinoma (PDAC). METHODS: PDAC guidelines published after 2015 were collected. Furthermore, a systematic search of the literature on postoperative surveillance was performed in PubMed and Embase from 2000 to 2019. Articles comparing different diagnostic modalities and frequencies of postoperative surveillance in PDAC patients with regard to survival, quality of life, morbidity and cost-effectiveness were selected. RESULTS: The literature search resulted in 570 articles. A total of seven guidelines and twelve original clinical studies were eventually evaluated. PDAC guidelines increasingly recommend a combination of tumor marker testing and computed tomography (CT) imaging every three to six months during the first two years after resection. These guidelines are, however, based on expert opinion and other low-level evidence. Prospective studies comparing different surveillance strategies are lacking. According to recent studies, surveillance with tumor markers and imaging at regular intervals results in the detection of PDAC recurrence before the onset of symptoms and more frequent administration of further therapy, such as chemotherapy or radiotherapy. CONCLUSION: Current evidence for recurrence-focused surveillance after PDAC resection is limited and contradictory. Consequently, recommendations on surveillance are conflicting. To define the clinical merit of recurrence-focused surveillance, patients who are most likely to benefit from early detection and treatment of PDAC recurrence need to be identified. To this purpose, well-designed prospective studies are needed, accounting for both economical and psychosocial implications of surveillance.

Four-dimensional stereotactic radiotherapy for early stage non-small cell lung cancer: a comparative planning study.

In this study we sought to assess the potential of the respiratory tumor tracking system of the CyberKnife to administer 3 fractions of 15 Gy in the treatment of early stage non-small cell lung cancer (NSCLC). The CyberKnife plans were compared to those developed for 3-D conformal radiotherapy (3-D CRT) administering 20 fractions of 3 Gy based on a slow CT. Ten patients with stage I NSCLC, who were previously treated with 3-D CRT, were re-planned with the CyberKnife treatment planning system. In the 3-D CRT plan, the planning target volume (PTV) included the gross tumor volume (GTV)(slow) and a 15-mm margin, whereas in the CyberKnife plan the margin was 8 mm. The physical doses from both treatment plans were converted to normalized total doses (NTD) using the linear quadratic model with an alpha/beta(tumor) of 10 Gy and alpha/beta(organs at risk (OAR)) of 3 Gy. The average minimal and mean doses administered to the PTV with the CyberKnife and 3-D CRT were 93 and 115.8 Gy and 61 and 66 Gy, respectively (p<0.0001). The mean V(20) of the CyberKnife and 3-D CRT plans were 8.2% and 6.8%, respectively (p=0.124). Both plans complied with the OAR constraints. In conclusion, 4-dimensional stereotactic radiotherapy can increase the minimal and mean biological dose with 51% and 75%, in comparison with 3-D CRT without significantly increasing the V(20), respectively.

Preoperative chemoradiation with capecitabine in locally advanced rectal cancer.

BACKGROUND: Preoperative radiation therapy in combination with 5-fluoracil (5-FU) improves local tumour control in locally advanced rectal cancer. The aim of our study was to evaluate the toxicity and efficacy of preoperative chemoradiation using the oral 5-FU prodrug capecitabine in locally advanced rectal cancer. METHODS: Sixty patients with locally advanced rectal cancer were treated with preoperative chemoradiation. Radiotherapy consisted of a total dose of 50 Gy delivered in 25 fractions to the pelvis. Chemotherapy was concurrently administered and consisted of oral capecitabine only on radiotherapy days. Surgery was performed six to ten weeks after completion of chemoradiation. RESULTS: The patient population consisted of 19 females and 41 males, with a median age of 61 years. All but two patients received the full dose of chemoradiation. No grade 3 or 4 haematological toxicities developed. Two patients (3%) developed grade 3 radiation dermatitis and one a grade 3 diarrhoea. All patients underwent definitive surgery; 19 patients underwent an abdominal perineal resection (APR), 25 a low anterior resection (LAR) and 16 patients a Hartmann's procedure. One patient with a low anterior resection developed an anastomotic leakage (4%). Final pathology demonstrated eight patients (13%) with a complete pathological response. Primary tumour and nodal downstaging occurred in 67 and 84% of the patients, respectively. Two patients (3%) had an R1 resection, one after an APR and one after an LAR. CONCLUSION: Preoperative chemoradiation with oral capecitabine is safe and well tolerated in locally advanced rectal cancer patients. This preoperative treatment has a considerable downstaging effect on the tumour and lymph nodes.

Esophagus toxicity after stereotactic and hypofractionated radiotherapy for central lung tumors: Normal tissue complication probability modeling.

PURPOSE: To correlate esophagus toxicity and dose-volume histogram (DVH) parameters in order to assess risks, and derive a Normal Tissue Complication Probability (NTCP) model. METHODS AND MATERIALS: Patients with a central lung tumor from 2 centers, who underwent stereotactic or hypofractionated radiotherapy (≤12 fractions), were analyzed. Doses were recalculated to an equivalent dose of 2 Gy with an α/ß ratio of 10 (EQD210). The esophagus was manually delineated and DVH-parameters (Dmax,EQD2, D1cc,EQD2, D2cc,EQD2, D5cc,EQD2) were analyzed and used for NTCP modeling based on logistic regression analysis. RESULTS: Two-hundred-and-thirty-one patients with 252 tumors were eligible. No acute or late grade 3-5 esophageal toxicity was reported. Acute grade 1-2 esophagus toxicity was recorded in 38 patients (17%). All DVH-parameters were significantly higher in patients with toxicity. NTCP models showed a 50% probability of acute grade 1-2 toxicity at a Dmax of 67 Gy EQD210 and D1cc of 42 Gy EQD210. No difference in overall survival was observed between patients with and without toxicity (p = 0.428). CONCLUSION: As no grade 3-5 esophageal toxicity was observed in our cohort, a Dmax of 56 Gy EQD210 and a D5cc of 35.5 Gy EQD210 could be delivered without high risks of severe toxicity. The NTCP models of this study might be used as practical guidelines for the treatment of central lung tumors with stereotactic radiotherapy.

Total pelvic exenteration for locally advanced and locally recurrent rectal cancer in the elderly.

BACKGROUND: Total pelvic exenteration (TPE) is a radical approach for locally advanced rectal cancer (LARC) and locally recurrent rectal cancer (LRRC) in case of tumour invasion into the urogenitary tract. The aim of this study is to assess surgical and oncological outcomes of TPE for LARC and LRRC in elderly patients compared to younger patients. METHODS: All patients who underwent TPE for LARC and LRRC between January 1990 and March 2017 were retrospectively analyzed. Patients aged <70 years were classified as younger and ≥70 years as elderly patients. RESULTS: In total 126 patients underwent TPE, of whom 88 younger and 38 elderly patients. Elderly patients had a significantly higher number of ASA > II patients (p = 0.01). Indication for surgery LARC (n = 73) and LRRC (n = 53) did not differ significantly. The 30-day mortality rate was significantly higher (p = 0.01) in elderly (13%) compared to younger patients (3%). Elderly patients experienced more anastomotic leakage (p = 0.02). Median overall survival (OS) was 75 months [95%CI 37.1; 112.9] for elderly and 45 months [95%CI 22.4; 67.8] for younger patients (p = 0.77). The 5-year OS rate was 44% in both groups. Median disease specific survival (DSS) was 78 months [95%CI 69.1; 86.9] for elderly and 60 months [95%CI 36.6; 83.4] for younger patients (p = 0.34). The 5-year DSS rate was 57% and 49%, respectively. CONCLUSION: TPE is an invasive treatment for rectal cancer with high 30-day mortality in elderly patients. Oncological outcomes are similar in elderly and younger patients. Therefore, TPE should not be withheld because of high age only, but careful patient selection is needed.