Lucia Giaccherini

Preoperative Chemoradiation With VMAT-SIB in Rectal Cancer: A Phase II Study

Purpose The aim of this study was to investigate the efficacy and toxicity of volumetric modulated arc therapy (VMAT)–simultaneous integrated boost (SIB) in preoperative combined treatment of locally advanced rectal cancer. Methods Radiation therapy was performed using the VMAT‐SIB technique. The dose to mesorectum and pelvic lymph nodes was 45 Gy (1.8 Gy/fraction). A concomitant boost was delivered on GTV + 2‐cm margin with a total dose of 57.5 Gy (2.3 Gy/fraction). The following concomitant chemotherapy was administered: capecitabine (825 mg/m2 twice daily, 5 days per week) and oxaliplatin (130 mg/m2 on days 1, 17, and 35). Efficacy was evaluated in terms of complete pathological response (pCR). Acute toxicities were evaluated according to Common Terminology Criteria for Adverse Events version 3.0 criteria. Results A total of 18 patients (7 women; median age 62 years; clinical stage: 4 local recurrences, 6 cT4, 5 cT3, 3 cT2, 2 cN0, 7 cN1, 9 cN2) were enrolled. Sixteen patients underwent surgical resection (9 low anterior resection, 6 abdominal perineal amputations; 1 transanal excision) and 2 patients did not undergo surgery for early metastatic progression or death from acute pulmonary edema. R0 resection was achieved in all patients who underwent surgery. Overall, 4 patients had a pCR and 7 patients only a microscopic residual of disease (pT0‐Tmic: 11/18 = 61.1%; 95% CI, 36.2‐86.1). Acute grade ≥ 3 toxicity was as follows: 1 case of leukopenia, 1 skin toxicity, 1 genitourinary toxicity, and 5 gastrointestinal toxicities, with an overall incidence of 8 (44.4%) of 18 patients. One‐, 3‐, and 5‐year cumulative local control was 100%, 68.6%, and 68.6%, respectively. One‐, 3‐, and 5‐year cumulative disease‐free survival was 88.9%, 66.7%, and 66.7%, respectively. One‐, 3‐, and 5‐year cumulative overall survival was 85%, 63.8%, and 63.8%, respectively. Conclusion The regimen used in this study showed excellent results in terms of pathologic responses. However, despite the use of the VMAT technique, more than one‐third of patients had severe acute toxicity. Micro‐Abstract The efficacy and toxicity of volumetric modulated arc therapy (VMAT)–simultaneous integrated boost (SIB) in preoperative combined treatment of locally advanced rectal cancer were investigated. VMAT‐SIB with concomitant capecitabine and oxaliplatin showed a good efficacy: 11 (61.1%) of 18 patients had complete or near complete response. Severe acute toxicity was not negligible and reported in 44.4% patients.

Time to surgery and pathologic complete response after neoadjuvant chemoradiation in rectal cancer: A population study on 2094 patients

Highlights • A large population based analysis to evaluate pathologic response according to time of surgery.• LARC patients were treated with modern techniques of radiotherapy and surgery.• The rate of pCR increased according to time interval from 12.6% to 31.1%.• The pCR increasing was 1.5% (about 0.2%/die) per each week of waiting.• Lengthening the interval (>13 weeks) significantly improved the pathological response.

Underuse of brachytherapy for the treatment of dysphagia owing to esophageal cancer. An Italian survey

BACKGROUND International guidelines strongly recommend brachytherapy as valid alternative or in addition to stenting in patients with dysphagia owing to esophageal cancer. However, for not well understood reasons, brachytherapy is definitively underused for the palliative treatment of malignant dysphagia. Aim of the current survey was to investigate the use of brachytherapy for the treatment of malignant dysphagia in Italy. METHODS A structured questionnaire was submitted to the 1510 members of the Italian Association of Radiation Oncologists (AIRO). These members refer to 177 centres of radiotherapy across Italy and in 68 (38.4%) of them brachytherapy is routinely performed. RESULTS Of the 1510 invited members, 178 completed the survey (11.7%). The answers provided by the 178 participants allowed to get information on 40 out of 68 brachytherapy centres (58.8%). Seven out of 40 (17.5%) centres perform brachytherapy of the oesophagus, in 3 out of 40 (7.5%) centres brachytherapy represents the first line of treatment. The main reason why brachytherapy is not routinely performed is the lack of experience. CONCLUSION Despite the strong recommendations of the international guidelines and the wide diffusion of brachytherapy centres across Italy, only very few of them routinely considered brachytherapy for the treatment of dysphagia due to esophageal cancer.

Prognostic Impact of Presurgical CA19-9 Level in Pancreatic Adenocarcinoma: A Pooled Analysis

BACKGROUND: Presurgical carbohydrate antigen 19-9 (CA19-9) level predicts overall survival (OS) in resected pancreatic adenocarcinoma (PaC). The aim of this pooled analysis was to evaluate if presurgical CA19-9 level can also predict local control (LC) and distant metastasis-free survival (DMFS). METHODS: Seven hundred patients with PaC from eight institutions who underwent surgical resection ± adjuvant treatment between 2000 and 2014 were analyzed. Patients were divided based on four presurgical CA19-9 level cutoffs (5, 37, 100, 353 U/ml). Weibull regression model to identify independent predictors of OS on 404 patients with complete information was fitted. RESULTS: Median follow-up was 17 months (range: 2-225 months). Univariate analysis showed a better prognosis in pT1-2, pN0, diameter <30 mm, or grade 1 tumors and in patients undergoing R0 resection, distal pancreatectomy, or adjuvant chemotherapy and with lower CA19-9 levels. Five-year OS, LC, and DMFS were as follows: CA19-9 <5.0: 5.7%, 47.2%, 17.0%; CA19-9 5.1-37.0: 37.9%, 63.3%, 46.0%; CA19-9 37.1-100.0: 27.1%, 59.4%, 39.0%; CA19-9 100.1-353.0: 17.4%, 43.4%, 26.7%; CA19-9 >353.1: 10.9%, 50.2%, and 23.4%, respectively. At multivariate analysis, CA19-9 >100 and <353 level (P=.002), CA19-9 ≥353.1 (P<.001) level, G3 tumor (P=.002), and tumor diameter >30 mm (P<.001) correlated with worse OS. Patients treated with postoperative chemoradiation doses >50.0 Gy showed improved OS (P<.001). CONCLUSION: Presurgical CA19-9 predicts both OS and pattern of failure. Therefore, CA19-9 should be included in predictive models in order to customize treatments based on prognostic factors. Moreover, future studies should stratify patients according to presurgical CA19-9 level.

Radiotherapy of pancreatic cancer in older patients: A systematic review

Pancreatic cancer (PaC) will soon be one of the main causes of cancer mortality. Furthermore, its incidence is higher in the older population and radiotherapy (RT) represents a treatment option. The aim of this review was to evaluate feasibility and outcome of RT in older patients with PaC. A systematic literature review of patients aged ≥65 years with PaC treated with RT was performed using the PRISMA methodology. Eleven papers (1830 patients) fulfilled our inclusion criteria and were analyzed. RT was prescribed either alone or as an adjuvant treatment. Prescribed RT dose ranged from 22.0 to 70.0 Gy with conventional fractionation or hypo-fractionated schedule and delivered by three-dimensional conformal RT, intensity modulated RT or stereotactic body RT. Grade ≥ 3 acute and grade ≥ 2 late toxicity rates ranged between 0.0% and 52.6% (median: 0.5%) and between 0.0% and 15.0% (median: 0%), respectively. Median overall survival and two-year survival rate were 11.3 months (range: 6.4-69.0 months) and 49.0% (range 6.6-75.5%), respectively. RT in older patients seems to be tolerable and safe particularly in terms of late toxicity irrespective of the treatment settings. Therefore, RT can represent a treatment option in PaC even in an older population. Further analyses and prospective trials enrolling older patients are needed to better define the risk/benefit ratio in different treatment settings.

Predictive factors of late-onset rectal mucosal changes after radiotherapy of prostate cancer

BACKGROUND/AIM The Vienna Rectoscopy Score (VRS; from 0, absence of rectal mucosal changes, to 5) assessed 1 year after radiotherapy is a surrogate end-point of late rectal toxicity. The aim of this study was to investigate the association between treatment-related factors and 1-year VRS. PATIENTS AND METHODS We performed a retrospective analysis of prospectively collected data. Patients with prostate adenocarcinoma treated with definitive or postoperative radiotherapy (RT) underwent endoscopy 1 year after RT. Relationships between VRS of 2 or more and treatment parameters were investigated by univariate and multivariate logistic analyses. RESULTS One hundred and ninety-five patients (mean age=69 years; range=43-81 years) were considered eligible for the study. At univariate analysis, patients treated with hypofractionation plus radiosurgery boost (p<0.001) and an equivalent dose in 2 Gy per fraction (EQD2) (α/β=3) ≥75 Gy (p<0.001) was associated with a significantly higher incidence of VRS ≥2 after 1 year of follow-up. At multivariate analysis, radiosurgery boost was an independent risk factor for developing rectal mucosal lesions (VRS ≥2), yielding an odds ratio (OR) of 4.14 (95% confidence interval (CI)=1.2-13.8), while pelvic surgery was inversely associated with VRS ≥2 (OR=0.39; 95% CI=0.17-0.94). CONCLUSION Hypofractionation followed by radiosurgery boost significantly increased the risk of developing late-onset rectal mucosal changes. Therefore, special care and preventative treatment strategies are needed when using radiosurgery boost after hypofractionated RT.

Clinical Target Volume Definition in Preoperative Radiotherapy of Rectal Carcinoma: a Systematic Review

Purpose of ReviewPreoperative radiotherapy (RT) or chemoradiation represents a standard option in neoadjuvant treatment of rectal cancer (RC). The aim of this analysis is to present a systematic review of clinical target volume (CTV) definition in preoperative RT of RC.A systematic review of published literature was performed. Studies providing clear indications for CTV definition in preoperative RT of RC were eligible. Only studies published as full text were considered. The search was restricted to English, German, and French languages. The CTV delineation, based on the different guidelines, was drawn on selected slices of a CT scan and the CTV definition based on different guidelines was reported in a table to facilitate the comparison.Recent FindingsA total of six publications containing indications for CTV delineation fulfilled the selection criteria and were included in our review. The studies showed a large variability in available indications between CTV contouring guidelines of RC, partly arising from differences in methods used to propose the single guidelines: expert opinion, systematic review, computer-generated consensus, and 3D modeling of recurrence sites.SummaryIn our systematic analysis, the available indications for CTV definition in preoperative RT of RC were reviewed. A large variation in target volume delineation was observed.

Dyspnoea in a 72-year-old woman.

A 72-year-old woman presented to our hospital, with progressive shortness of breath and dry cough for 3 months. She denied fever and had no symptoms of cardiopulmonary involvement. She had a history of hypertension. In 2009, the patient had a sigmoid colon carcinoma with synchronous single liver metastasis; both lesions were surgically treated followed by chemotherapy. In 2011, a diagnosis of metachronous solitary lung metastasis was made and a lobectomy performed. On admission, the patients …