Dajana Cuicchi

Prospective study on the FDG–PET/CT predictive and prognostic values in patients treated with neoadjuvant chemoradiation therapy and radical surgery for locally advanced rectal cancer

BACKGROUND 2-[fluorine-18]fluoro-2-deoxy-D-glucose-positron emission tomography/computed tomography (FDG-PET/CT) was carried out before and after neoadjuvant chemoradiotherapy (NCRT) followed by radical surgery for locally advanced rectal cancer (LARC). The aim of this study was to define its predictive and prognostic values. PATIENTS AND METHODS Patients with cT3-T4 N-/+ carcinoma of medium/low rectum received daily 5-fluorouracil-based chemotherapy infusion and radiation therapy on 6-week period followed by surgery 7-8 weeks later. Tumour metabolic activity, expressed as maximum standardised uptake value (SUV-1 = at baseline and SUV-2 = pre-surgery), was calculated in the most active tumour site. Predictive and prognostic values of SUV-1, SUV-2 and Δ-SUV (percentage change of SUV-1 - SUV-2) were analysed towards pathological response (pR) in the surgical specimen and disease recurrence, respectively. RESULTS Eighty consecutive patients entered the study. SUV-1, SUV-2 and Δ-SUV appeared singly correlated with pR, but not one of them resulted an independent predictive factor at multivariate analysis. After a median follow-up of 44 months, 13 patients (16.2%) presented local and/or distant recurrence. SUV-2 ≤5 was associated with lower incidence of disease recurrence and resulted prognostic factor at multivariate analysis. CONCLUSIONS Dual-time FDG-PET/CT in patients with LARC treated with NCRT and radical surgery supplies limited predictive information. However, an optimal metabolic response appears associated with a favourable patient outcome.

Patient-reported outcomes after neoadjuvant chemoradiotherapy for rectal cancer: a multicenter prospective observational study.

Objective:To prospectively describe patient-reported outcomes (PROs) after preoperative chemoradiotherapy (pCRT) for rectal cancer. Background:Little evidence is available on PROs after pCRT for rectal cancer. Patients and Methods:Patients with rectal cancer, candidates to receive pCRT, were enrolled in a multicenter prospective observational trial. Health-related quality of life was assessed using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and its colorectal cancer module (QLQ-CR38), and fecal incontinence and bowel function were evaluated using the fecal incontinence score questionnaire and a set of ad hoc questions. Questionnaires were filled out before CRT (t0), 2 to 3 weeks after completion of CRT (t1), and at 6 (t2) and 12 months (t3) after surgery. Primary analysis of selected scales included: global quality of life, physical functioning, social functioning, fatigue, body image, future prospective, and gender-related sexual problems. Results:Of 149 eligible patients, questionnaires were completed in 100%, 95%, 88% and 77% of cases at t0, t1, t2, and t3, respectively. At t3, 78% of patients reported stool fractionation and 72% sensation of incomplete defecation. Only 14% of patients had optimal continence. Physical/social functioning, fatigue, and body image showed a decrease just after pCRT and returned to baseline levels at 1 year after treatment. Global quality of life was stable over time. Male sexual problems were greatly impaired throughout the study period (P < 0.001) with major clinically meaningful changes between baseline and 1 year after treatment. Conclusions:These findings add to the body of evidence available regarding pCRT and help clinicians to make more informed treatment decisions.

Clinical and instrumental evaluation of pelvic floor disorders before and after bariatric surgery in obese women.

BACKGROUND Obesity, well known as a risk factor for several diseases, can also lead to pelvic floor dysfunction (PFD). However, scant data are available regarding PFD in obese individuals. Our study was designed to assess the prevalence, severity, and the quality of life (QOL) effect of PFD in obese women before and after bariatric surgery at a university hospital in Italy. METHODS A total of 100 obese (body mass index [BMI] ≥30 kg/m(2)) women completed 6 validated specific and QOL questionnaires about PFD. The patients were evaluated by physical examination, endoanal ultrasonography, rectal balloon distension test, and dynamic magnetic resonance imaging. Of the 100 patients, 87 were reassessed 12 months after bariatric surgery. RESULTS The prevalence of PFD was 81%, and 49% of patients reported that their symptoms adversely affected their QOL. Urinary incontinence (UI) was the most common disorder (61%) and was associated with the BMI (P = .04). Fecal incontinence and pelvic organ prolapse symptoms were reported by 24 and 56 patients, respectively. Urogenital prolapse and rectocele was documented in 15% and 74% of patients, respectively. After a mean BMI reduction of 10 kg/m(2), the prevalence of PFD decreased to 48% (P = .02), with a significant improvement in QOL. The prevalence of UI decreased to 9.2% (P = .0001) and was associated with the decrease in postoperative BMI (P = .04). The rate of resolution of the symptoms was 84%, 85%, and 74% for UI, fecal incontinence, and pelvic organ prolapse, respectively. CONCLUSION In the present sample of obese women, PFD was common and adversely affected their QOL. A clear association was found between the BMI and UI. Weight loss resulted in improved UI, fecal incontinence, and symptoms of pelvic organ prolapse.

Mortality and Morbidity

Historically, morbidity and mortality rates related to surgery for locally recurrent rectal cancer (LRRC) have been >70% and 30%, respectively [1, 2, 3]. Because of the excessive operative risks, the benefit of such resections has been questioned and — although radical operation for LRRC was conceptualized and reported more than 60 years ago — for years it has not been accepted as being standard procedure. More appropriate selection of candidates for resection due to advances in imaging modalities, improvement in surgical techniques, establishment of specialized multidisciplinary surgical teams, and improvement in quality of perioperative management have resulted in better outcomes in recent years. Currently, mortality rates vary between 0–5% at 1 month and 8% at 3 months [4]. The causes of death are mainly disseminated coagulopathies related to prolonged sepsis and blood loss, multiorgan failure, cardiac events, and pulmonary embolism [5, 6]. Morbidity remains significant, ranging from 15 to 68%, and increases with the complexity of resection [7, 8, 9, 10]. Bleeding is the main and most severe intraoperative complication, and occurs in 0.2–9% of cases, and related mortality is high (4%) [11, 12, 13, 14]. The principal postoperative complications include pelvic abscess (7–50%), intestinal obstruction (5–10%), enterocutaneous or enteroperineal fistulas (1.2%), perineal wound dehiscence (4–24%), and cardiovascular, renal, and pulmonary complications (1–20%) [5, 7, 8].

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.

Treatment Strategy for Rectal Cancer with Synchronous Metastasis: 65 Consecutive Italian Cases from the Bologna Multidisciplinary Rectal Cancer Group

Background: Twenty percent of rectal cancer patients have synchronous distant metastasis at diagnosis. At present, the treatment strategy in this patient setting is not well defined. This study in one institution evaluates the treatment strategy of three different patient groups. Patients and Methods: Between January 2000 and July 2011, 65 patients with M1 rectal cancer were evaluated. Three different groups were defined: rectal cancer with resectable metastatic disease (group A); rectal cancer with potentially resectable metastatic disease (group B), and rectal cancer with unresectable metastatic disease (group C). Results: Group A included 11 patients (16.9%), group B 28 patients (43.1%) and group C 26 patients (40%). Forty-three (66.2%) patients underwent surgery for primary rectal cancer, and 30 (46.2%) patients for metastasis resection (23 liver, 4 lung and 3 ovary). Median overall survival (OS) by group was: 51 (5-86; group A), 32 (24-40; group B) and 16 (7-26; group C) months. Patients undergoing metastasis resection have higher median OS than unresected patients (44 vs. 15 months; p < 0.001). Conclusions: The treatment strategy in synchronous metastatic rectal cancer must consider the possibility of distant metastasis resection. Long-term survival can be achieved using an integrated approach.

Neoadjuvant chemoradiation for rectal cancer in patients aged 75 years or older

Background Preoperative chemoradiotherapy (CRT) has been widely adopted as the standard of care for locally advanced rectal cancer in most western countries. However there has been a general exclusion of the elderly patients from neoadjuvant trials often due to concerns over their tolerance of surgery and/or (chemo)radiotherapy. Our aim was to compare the compliance to preoperative CRT of rectal cancer patients aged ≥75 years and younger.

Simultaneous curative resection of double colorectal carcinoma with synchronous bilobar liver metastases

Synchronous colorectal carcinoma (SCRC) indicates more than one primary colorectal carcinoma (CRC) discovered at the time of initial presentation, accounts for 3.1%-3.9% of CRC, and may occur either in the same or in different colorectal segments. The accurate preoperative diagnosis of SCRC is difficult and diagnostic failures may lead to inappropriate treatment and poorer prognosis. SCRC requires colorectal resections tailored to individual patients, based on the number, location, and stage of the tumours, from conventional or extended hemicolectomies to total colectomy or proctocolectomy, when established predisposing conditions exist. The overall perioperative risks of surgery for SCRC seem to be higher than for solitary CRC. Simultaneous colorectal and liver resection represents an appealing surgical strategy in selected patients with CRC and synchronous liver metastases (CRLM), even though the cumulative risks of the two procedures need to be adequately evaluated. Simultaneous resections have the noticeable advantage of avoiding a second laparotomy, give the opportunity of an earlier initiation of adjuvant therapy, and may significantly reduce the hospital costs. Because an increasing number of recent studies have shown good results, with morbidity, perioperative hospitalization, and mortality rates comparable to staged resections, simultaneous procedures can be selectively proposed even in case of complex colorectal resections, including those for SCRC and rectal cancer. However, in patients with multiple bilobar CRLM, major hepatectomies performed simultaneously with colorectal resection have been associated with significant perioperative risks. Conservative or parenchymal-sparing hepatectomies reduce the extent of hepatectomy while preserving oncological radicality, and may represent the best option for selected patients with multiple CRLM involving both liver lobes. Parenchymal-sparing liver resection, instead of major or two-stage hepatectomy for bilobar disease, seemingly reduces the overall operative risk of candidates to simultaneous colorectal and liver resection, and may represent the most appropriate surgical strategy whenever possible, also for patients with advanced SCRC and multiple bilobar liver metastases.

Evolving role of FDG-PET/CT in prognostic evaluation of resectable gastric cancer

Gastric cancer (GC) remains a leading cause of cancer death worldwide. Radical gastrectomy is the only potentially curative treatment, and perioperative adjuvant therapies may improve the prognosis after curative resection. Prognosis largely depends on the tumour stage and histology, but the host systemic inflammatory response (SIR) to GC may contribute as well, as has been determined for other malignancies. In GC patients, the potential utility of positron emission tomography/computed tomography (PET/CT) with the imaging radiopharmaceutical 18F-fluorodeoxyglucose (FDG) is still debated, due to its lower sensitivity in diagnosing and staging GC compared to other imaging modalities. There is, however, growing evidence that FDG uptake in the primary tumour and regional lymph nodes may be efficient for predicting prognosis of resected patients and for monitoring tumour response to perioperative treatments, having prognostic value in that it can change therapeutic strategies. Moreover, FDG uptake in bone marrow seems to be significantly associated with SIR to GC and to represent an efficient prognostic factor after curative surgery. In conclusion, PET/CT technology is efficient in GC patients, since it is useful to integrate other imaging modalities in staging tumours and may have prognostic value that can change therapeutic strategies. With ongoing improvements, PET/CT imaging may gain further importance in the management of GC patients.

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.