Multiparametric imaging guided HDR interventional radiotherapy (brachytherapy) boost in localized prostate cancer: a multidisciplinary experience.

OBJECTIVE: The aim of this study was to report a monoinstitutional multidisciplinary experience about the use of multiparametric imaging to identify the areas with higher risk of relapse in localized prostate cancer, with the purpose of allowing a biologically planned target dose escalation. PATIENTS AND METHODS: We performed a retrospective evaluation of patients diagnosed with prostate cancer who received treatments at our Interventional Oncology Center with interstitial interventional radiotherapy from 2014 to 2022. Inclusion criteria were histologically confirmed localized prostate cancer; and National Comprehensive Cancer Network (NCCN) risk class unfavorable intermediate or high/very high risk. The diagnostic work-up included multiparametric Magnetic resonance imaging (MRI), multiparametric Transrectal ultrasound (TRUS), Positron Emission Tomography Computed Tomography (PET-CT) with choline or PSMA (or alternatively bone scan). All patients were assessed and received one treatment with interstitial high-dose-rate interventional radiotherapy (brachytherapy) delivering external beam radiotherapy (46 Gy). All procedures were performed using transrectal ultrasound guidance under general anesthesia and the prescribed doses were 10 Gy to the whole prostate, 12 Gy to the peripheral zone and 15 Gy to the areas at risk. RESULTS: We report the data of 21 patients who were considered for the statistical analysis with a mean age of 62.5 years. The mean PSA nadir was 0.03 ng/ml (range 0-0.09). So far, no biochemical nor radiological recurrences have been recorded in our series. Regarding acute toxicity, the most commonly reported side effects were G1 urinary in 28.5% of patients and G2 urinary in 9.5%; all recorded acute toxicities resolved spontaneously. CONCLUSIONS: We present a real-life experience of biologically planned local dose escalation by interventional radiotherapy (brachytherapy) boost, followed by external beam radiotherapy in patients with intermediate unfavorable- or high/very high risk. The local control and the biochemical control rates are proved to be excellent and the toxicity profile tolerable.

The ten commandments of chemoembolization: expert discussion and report from Mediterranean Interventional Oncology (MIOLive) congress 2017.

Transarterial therapies in the setting of primary and secondary liver malignancies are becoming an essential part of the oncology landscape. The mechanism of action of c-TACE is the induction of tumor necrosis due to the high concentration of the chemotherapeutic that is delivered only locally and to the embolic effect that causes ischemia and increased dwell time of the chemotherapeutic in the tumor. Recently, DEB-TACE has emerged as a variation of c-TACE with the potential for the selective delivery of large amounts of drugs to the tumor for a prolonged period, thereby decreasing plasma levels of the chemotherapeutic agent and related systemic effects. There is an increasing consensus that compared with conventional lipiodol-based regimen, DEB-TACE offers standardized methodology, is more reproducible and is associated with improved response and significantly better safety profile. Using an easy to access point by point format, this manuscript summarizes the expert discussion from the Mediterranean Interventional Oncology Live Congress (MIOLive 2017) about the role of TACE in the treatment of liver tumors.

Postoperative chemotherapy in patients with rectal cancer receiving preoperative radio(chemo)therapy: A meta-analysis of randomized trials comparing surgery ± a fluoropyrimidine and surgery + a fluoropyrimidine ± oxaliplatin.

BACKGROUND: There is no consensus on the role of postoperative chemotherapy in patients with rectal cancer who have received preoperative radio(chemo)therapy. MATERIALS AND METHODS: A systematic review and meta-analysis were performed of trials that used preoperative radio(chemo)therapy and randomized patients either between postoperative chemotherapy and observation or between a fluoropyrimidine only (FU-only) and a fluoropyrimidine with oxaliplatin (FU-OXA) as postoperative chemotherapy. RESULTS: Five randomized studies compared postoperative chemotherapy with observation in a total of 2398 patients. None of these trials demonstrated a statistically significant benefit of chemotherapy for OS and DFS. The pooled differences in OS and DFS did not differ statistically significantly between the chemotherapy group and the observation group. The hazard ratios (HRs) and 95% confidence intervals (CIs) were 0.95 (CI: 0.82-1.10), P = 0.49 and 0.92 (CI: 0.80-1.04), P = 0.19, respectively. In the subgroup of trials in which randomization was performed after surgery (n = 753), a statistically significant positive pooled chemotherapy effect was observed for DFS (HR = 0.79, 95% CI: 0.62-1.00, P = 0.047), but not for OS (P = 0.39). Four randomized trials compared adjuvant FU-OXA with adjuvant FU-only in 2710 patients. In two trials, the difference in DFS between groups was statistically significant in favour of FU-OXA, and in the other two trials, the difference was not significant. The pooled difference in DFS between the FU-OXA group and the FU-only group was not statistically significant: HR = 0.84 (CI: 0.66-1.06), P = 0.15. CONCLUSION: The use of postoperative chemotherapy in patients with rectal cancer receiving preoperative radio(chemo)therapy is not based on strong scientific evidence.

EURECCA consensus conference highlights about colon & rectal cancer multidisciplinary management: the radiology experts review.

Some interesting shifts have taken place in the diagnostic approach for detection of colorectal lesions over the past decade. This article accompanies the recent EURECCA consensus group reccomendations for optimal management of colon and rectal cancers. In summary, imaging has a crucial role to play in the diagnosis, staging assessment and follow up of patients with colon and rectal cancer. Recent advances include the use of CT colonography instead of Barium Enema in the diagnosis of colonoic cancer and as an alternative to colonoscopy. Modern mutlidetector CT scanning techniques have also shown improvements in prognostic stratification of patients with colonic cancer and clinical trials are underway testing the selective use of neoadjuvant therapy for imaging identified high risk colon cancers. In rectal cancer, high resolution MRI with a voxel size less or equal to 3 × 1 × 1 mm3 on T2-weighted images has a proven ability to accurately stage patients with rectal cancer. Moreover, preoperative identification of prognostic features allows stratification of patients into different prognostic groups based on assessment of depth of extramural spread, relationship of the tumour edge to the mesorectal fascia (MRF) and extramural venous invasion (EMVI). These poor prognostic features predict an increased risk of local recurrence and/or metastatic disease and should form the basis for preoperative local staging and multidisciplinary preoperative discussion of patient treatment options.

[Multidisciplinary management of rectal cancer]. / État des lieux du traitement multidisciplinaire du cancer du rectum.

In the last 10 years, a number of important European randomized published studies investigated the optimal management of rectal cancer. In order to define an evidence-based approach of the clinical practice based, an international consensus conference was organized in Italy under the endorsement of European Society of Medical Oncology (ESMO), European Society of Surgical Oncology (ESSO) and European Society of Therapeutic Radiation Oncology (ESTRO). The aim of this article is to present highlights of multidisciplinary rectal cancer management and to compare the conclusions of the international conference on 'Multidisciplinary Rectal Cancer Treatment: looking for an European Consensus' (EURECA-CC2) with the new National Comprehensive Cancer Network (NCCN) guidelines.

Nutritional counselling and oral nutritional supplements in head and neck cancer patients undergoing chemoradiotherapy.

BACKGROUND: The role of nutritional counselling (NC) with or without oral nutritional supplements (ONS) in patients receiving chemoradiotherapy (CRT) for head and neck cancer (HNC) still remains to be clearly defined, particularly with regard to CRT-related toxicity. METHODS: Patients undergoing CRT for HNC received NC by the dietitian within the first 4 days of radiotherapy and weekly for the course of radiotherapy (approximately 6 weeks). A weekly supply of oral nutrition supplements [1560 kJ (373 kcal) per 100 g] for up to 3 months was provided to all patients. RESULTS: Twenty-one patients completed CRT. Mucositis G3 developed in seven (33.3%) patients, whereas mucositis G4 was absent. Dysphagia was present before the start of treatment in four patients. In the remaining 17 patients, dysphagia G3 developed during/at the end of treatment in five cases. The percentage of patients interrupting anti-neoplastic treatment for was 28% for ≥6 days, 28% for 3-5 days and 44% for 0-2 days. Mucositis G3 frequency was lower in patients with a baseline body mass index (BMI, kg m(-2) ) ≥25 (two out of 12; 16.6%) than in patients with BMI <25 (five out of nine; 55.5%) (P = 0.161) and in patients with a baseline mid arm circumference >30 cm than in those with a mid arm circumference in the range 28.1-30 cm and <28 cm, and higher in patients with a greater weight loss and a greater reduction of serum albumin and mid arm circumference. CONCLUSIONS: Nutritional counselling and ONS are associated with relatively low CRT-related toxicity and with mild deterioration of nutritional parameters.

A phase I/II trial of three-dimensionally planned concurrent boost radiotherapy and protracted venous infusion of 5-FU chemotherapy for locally advanced rectal carcinoma.

BACKGROUND: Improving the response to preoperative therapy may increase the likelihood of successful resection of locally advanced rectal cancers. Historically, the pathologic complete response (pCR) rate has been < approximately 10% with preoperative radiation therapy alone and < approximately 20% with concurrent chemotherapy and radiation therapy. METHODS AND MATERIALS: Thirty-seven patients were enrolled on a prospective Phase I/II protocol conducted jointly at Washington University, St. Louis and the Catholic University of the Sacred Heart, Rome evaluating a three-dimensionally (3D) planned boost as part of the preoperative treatment of patients with unresectable or recurrent rectal cancer. Preoperative treatment consisted of 4500 cGy in 25 fractions over 5 weeks to the pelvis, with a 3D planned 90 cGy per fraction boost delivered once or twice a week concurrently (no time delay) with the pelvic radiation. Thus, on days when the boost was treated, the tumor received a dose of 270 cGy in one fraction while the remainder of the pelvis received 180 cGy. When indicated, nonaxial beams were used for the boost. The boost treatment was twice a week (total boost dose 900 cGy) if small bowel could be excluded from the boost volume, otherwise the boost was delivered once a week (total boost dose 450 cGy). Patients also received continuous infusion of 5-fluorouracil (1500 mg/m(2)-week) concurrently with the radiation as well as postoperative 5-FU/leucovorin. RESULTS: All 37 patients completed preoperative radiotherapy as planned within 32--39 elapsed days. Twenty-seven underwent proctectomy; reasons for unresectability included persistent locally advanced disease (6 cases) and progressive distant metastatic disease with stable or smaller local disease (4 cases). Actuarial 3-year survival was 82% for the group as a whole. Among resected cases the 3-year local control and freedom from disease relapse were 86% and 69%, respectively.Twenty-four of the lesions (65%) achieved an objective clinical response by size criteria, including 9 (24%) with pCR at the primary site (documented T0 at surgery). The most important factor for pCR was tumor volume: small lesions with planning target volume (PTV) < 200 cc showed a 50% pCR rate (p = 0.02). There were no treatment associated fatalities. Nine of the 37 patients (24%) experienced Grade 3 or 4 toxicities (usually proctitis) during preoperative treatment. There were an additional 7 perioperative and 2 late toxicities. The most important factors for small bowel toxicity (acute or late) were small bowel volume (> or = 150 cc at doses exceeding 4000 cGy) and large tumor (PTV > or = 800 cc). For rectal toxicity the threshold is PTV > or = 500 cc. CONCLUSION: 3D planned boost therapy is feasible. In addition to permitting the use of nonaxial beams for improved dose distributions, 3D planning provides tumor and normal tissue dose-volume information that is important in interpreting outcome. Every effort should be made to limit the treated small bowel to less than 150 cc. Tumor size is the most important predictor of response, with small lesions of PTV < 200 cc most likely to develop complete responses.

Topical issues in the treatment of rectal cancer: economic and organizational aspects of concomitant radiochemotherapy.

Concomitant radiochemotherapy in patients with locally advanced rectal carcinoma has been shown to be useful in improving local control and survival in operated patients and in favoring sphincter preservation when administered before surgery. Together with the search for less toxic combinations, cost-analysis of radiochemotherapy has become topical also in consideration of new generation drugs. In this study the analysis was carried out by comparing the costs for 4 different combined modalities in the dual perspective of the payer (the National Health Service) and the provider (the Hospital). Based on their characteristic of treatment and innovative aspects, the following combinations were examined: external beam radiotherapy (ERT) 50.4 Gy + 5FU bolus; ERT 50.4 Gy + 5FU protracted infusion; ERT 50.4 Gy + 5FU continuous infusion, week 1 and 5; ERT 50.4 Gy+ Tomudex bolus. Costs were evaluated based on the frequency and type of specific services provided in therapeutic protocols: the positioning of central venous catheter, time of stay in day-hospital or hospital ward and the cost of drugs. Calculations were carried out based on an "ideal" patient of 1.7 sqm body surface. Costs were based on out patient rates, DRGs and the official drug list valid to September 1999. As for day-hospital costs afforded by the payer it is observed that the most expensive combinations are bolus and continuous infusion followed by protracted infusion; Tomudex, is the most economic. As for hospital costs afforded by the provider, it is observed that the most expensive combination is continuous infusion followed by protracted infusion, bolus administration and Tomudex. In conclusion, doctors are increasingly involved in the economic and organizational aspects of therapeutic decisions; however, the patient's needs should be kept in mind; apart from the therapeutic benefits, lower toxicity and ready use of treatments are amongst the patient's needs. The analysis of the patient's satisfaction is still lacking suitable means of evaluation, however it should be defined and carefully studied for an exhaustive evaluation of the impact of combined modality therapy.

Chemoradiation with or without intraoperative radiation therapy in patients with locally recurrent rectal carcinoma: prognostic factors and long term outcome.

BACKGROUND: Rectal carcinoma patients with local recurrence are reported to have a dismal prognosis. The purpose of this study was to evaluate the effect of combined modality therapy on clinical outcome and to determine the prognostic impact of a "presurgical" staging system. METHODS: Between September 1989 and June 1997, 47 patients (with a median follow-up of 80 months) with locally recurrent, nonmetastatic rectal carcinoma were classified according to the extent of pelvic sidewall involvement as determined by pretreatment computed tomography (CT) scan. They received preoperative external beam radiation (45-47 grays [Gy] in 34 patients; 23.4 Gy in 13 preirradiated patients) plus concomitant 5-fluorouracil (1000 mg/m(2)/day as a 96-hour continuous infusion on Days 1-4 + 29-32) and mitomycin C (10 mg/m(2) as a bolus intravenously on Day 1 + 29). After 4-6 weeks, the patients were evaluated for surgical resection and intraoperative radiation therapy (IORT) procedure (10-15 Gy) or, in unresectable patients, a boost dose was planned by chemoradiation (23.4 Gy) or brachytherapy. Thereafter, adjuvant chemotherapy (5-fluorouracil and leucovorin for a total of six to nine courses) was prescribed. RESULTS: During chemoradiation, 2 patients (4.3%) developed Radiation Therapy Oncology Group Grade 3-4 acute toxicity. Twenty-five patients (53. 2%) had an objective response after chemoradiation. Twenty-one patients (45%) underwent radical surgical resection. The overall 5-year survival and local control rates were 22% and 32%, respectively. The classification system significantly predicted survival (P = 0.008). Radically resected patients had better local control and survival (P < 0.0001); in patients treated with IORT, the 5-year local control and survival rates were 79% and 41%, respectively. CONCLUSIONS: The data from the current study suggest that combined modality therapy was well tolerated and improved resectability, local control, and survival. The classification system appears to be a reliable tool with which to predict clinical outcome in patients with locally recurrent rectal carcinoma.

Intraoperative radiation therapy in integrated treatment of rectal cancers. Results of phase II study.

PURPOSE: Risk of local recurrence of rectal cancer remains high despite extensive therapeutic strategies, many of which have been tried to achieve better local control (i.e., external beam radiation therapy (EBRT)). Recently, intraoperative radiation therapy (IORT) has been introduced in clinical protocols to boost the areas at risk of local recurrence. METHODS: Between April 1990 and December 1995, 44 patients with "high risk" (T3,N0-2 primary tumors) extraperitoneal rectal tumors and 24 patients with "locally advanced" (2 T3,N3 and 11 T4,N0-3 primary tumors; 11 local recurrences) tumors entered a protocol that included preoperative EBRT (38 Gy), surgery plus IORT (10 Gy) in the high-risk group, and preoperative EBRT (45-48 Gy) and concomitant computerized tomography (5-fluorouracil plus mitomycin C), surgery plus IORT (10-15 Gy), and postoperative adjuvant computerized tomography (5-fluorouracil plus folinic acid) in the locally advanced group. RESULTS: In the high-risk group, acute Grade 3 (Radiation Therapy Oncology Group scale) skin toxicity, attributable to preoperative treatment, involved one patient (2.2 percent); among locally advanced cases, Grade 3 hematologic toxicity was observed in one patient (4.1 percent). Treatment was discontinued in no patients. On average, IORT prolonged surgery by 48 minutes. There was no mortality. Four anastomotic leakages, one pelvic infection, and five wound infections were observed. No chronic IORT-related toxicity occurred. After mean follow-up periods of 28.3 and 25.9 months, 41 and 15 patients in the high-risk and locally advanced groups, respectively, are alive and disease-free. In one high-risk patient, an anastomotic recurrence occurred. In four patients with locally advanced tumors (1 T4 primary, 3 local recurrences) an unresectable tumor relapse developed locally. Distant metastases occurred in two high-risk patients and in eight patients with a locally advanced tumor. Three-year actuarial survival was 100 percent in both high-risk and locally advanced primary tumors and 68.2 percent in local recurrences. CONCLUSIONS: Results of this study suggest that multimodal treatment (including IORT) in rectal cancer is safe, has no significant increase of mortality and morbidity, and also shows a trend for local improvement. A longer term follow-up and larger numbers of patients could demonstrate the therapeutic efficacy of IORT in rectal cancer.

Carcinoma of the pancreatic head area. Therapy: concomitant radiochemotherapy.

A series of studies carried out by the Gastrointestinal Tumor Study Group have shown the efficacy of the combination of external beam radiotherapy (ERT) and 5-fluorouracil (5-FU) chemotherapy (CHEM) in unresectable and resectable tumors of the exocrine pancreas. In the former in particular, this method was shown to be superior to ERT alone as well as to polychemotherapy alone. In these studies 5-FU was administered during (concomitant chemotherapy: C-CHEM) or after ERT (adjuvant chemotherapy: A-CHEM). This led several authors to consider this combined treatment as reference standard for pancreatic carcinoma. Its prognosis is still definitely poor because of the difficult local eradication as well as because of the frequent early distant spread, especially at the abdominal level (hepatic and peritoneal). An improvement of present results may stem from the combination of ERT+C-CHEM +/- A-CHEM with methods of dose intensification at the local level (e.g. IORT) concurrently with the use of treatments aiming at a better control of the abdominal spread (e.g. ERT+C-CHEM for prophylaxis of the liver or upper abdomen).

Combined modality staging of high risk rectal cancer.

The personal experience with the radiologic staging of high risk rectal cancer undergoing preoperative treatment is reported. 61 patients shown to be affected by locally advanced (T3-T4, N+with any T) rectal tumors on combined modality staging, underwent restaging 4-5 weeks after treatment. In all patients liver US, pelvic CT and colorectal enema were performed before and after treatment. In 22 patients with low rectal cancer transrectal sonography was performed. In 19 patients pelvic MRI was performed. The 61 patients were considered operable on second staging and thus referred to surgery. Subsequent control on histology has confirmed the diagnostic accuracy of the single procedures and of their combination. US was shown to be of high accuracy in the evaluation of T (90.8%) and of high predictive value for N. CT accuracy (84%) and MRI accuracy (78.9%) was lower because both tend to overstaging in the evaluation of T of rectal tumors undergoing preoperative treatment. Low CT accuracy (64%) and MRI accuracy (58%) was observed for N. There was optimum agreement between histology and imaging in the assessment of tumor shrinkage, well visualized by rectal enema which supported combined restaging with 88% accuracy for T.

Radiotherapy in rectal cancer: stage of the disease and therapeutic approach.

Rectal cancer requires treatments tailored according to the stage of the disease at diagnosis. In stage I lesions exclusive surgery is the elective treatment. Radiotherapy is used in those cases where the site of the lesion would sacrifice sphincter function. When the features of neoplasm are favourable (size < 5 cm, grading 1-2, histological type adenocarcinoma) local excision and postoperative radiotherapy enable to achieve results comparable to those of radical surgery. In operable lesions (T3-T4 (vagina) N0-2, M0) at high risk for local recurrence, high dose preoperative radiotherapy in some randomized studies has shown a significant improvement in local control and survival with a low toxicity, especially in patients undergoing radical surgery. Concomitant chemotherapy in postoperative radiotherapy has significantly improved local control and survival as compared to radiotherapy alone. Continuous infusion appears to reduce the toxicity, which is otherwise high. Randomized studies of preoperative radiochemotherapy vs radiation alone or vs postoperative radiochemotherapy are in progress in various Centers. Intensification with radiotherapy alone (IORT, fractionation) is also under study. In lesions unresectable for cure (T4, N0-3, M0) radiotherapy alone or combined with surgery did not show significant results. Intensification with concomitant chemotherapy and/or with IORT has enabled over 70% local control and 50% 5-year survival.

Clinical staging of rectal cancer. Results of a prospective continuing study.

78 patients with rectal adenocarcinoma were studied with a diagnostic protocol in order to obtain a TNM clinical stage in the preoperative period. Each patient underwent digital rectal examination, proctoscopy, double contrast barium enema, pelvic CT scan, liver ultrasound and chest x-ray. The degree of infiltration of the rectal wall by the tumor and the presence or absence of node and liver metastases were evaluated. After resection all specimens were studied by a pathologist who defined the pathologic stage. Data obtained by each diagnostic procedure were compared with the pathologic data. For each method, accuracy, specificity and sensitivity were evaluated. Each method showed an equivalent accuracy (100%) to detect infiltration of the muscularis of the rectum. Data were less accurate in identifying extraparietal tumor invasion. Accuracy was 79% for rectal examination, 74% for double contrast barium enema and 72% for pelvic CT scan. In the evaluation of lymph-node involvement, accuracy was 77%, specificity 74% and sensitivity 80%. Liver metastases were detected with 94% accuracy, 97% specificity and 50% sensitivity.