Palliative short-course radiotherapy (RAPASH study) in patients with rectal cancer.

Background: Palliative radiation therapy (RT) is used to treat symptomatic rectal cancer although clinical benefits and toxicities are poorly documented. There is no consensus about the optimal RT regimen and clinical practice undergoes significant changes. Our aim was to evaluate the efficacy and toxicity of short-course (SC) RT in this setting of patients. Materials and methods: Charts from patients with locally advanced disease not candidates for standard treatment or with symptomatic metastatic rectal cancer treated with SCRT (25 Gy/5 fractions in 5 consecutive days) were retrospectively reviewed. Clinical outcome measures were symptomatic response rate and toxicity. Results: From January 2007 to December 2017, 59 patients (median age 80 years) received SCRT; 53 were evaluable. The median follow-up was 8 months (range, 1-70). Clinical response to RT for bleeding, pain and tenesmus was 100%, 95% and 89%, respectively. The compliance with the treatment was 100% and no patient experienced acute severe (≥ grade 3) toxicities. Median time to symptoms recurrence was 11 months (range 3-69). Globally, the median overall survival was 12 months. Conclusions: SCRT is a safe and effective regimen in symptomatic rectal cancer and may be considered the regimen of choice for standard treatment in unfit patients.

Pleurodesis with Thulium Cyber Laser versus talc poudrage: a comparative experimental study.

Sclerosing fluids to achieve pleurodesis could be hardly replaced for bed-side procedures, but other devices may be successfully applied during thoracoscopy. Thulium Cyber Laser was experimented for this purpose and compared to talc poudrage. Twenty pigs underwent operative videothoracoscopy (VATS). Ten models were subjected to double-port VATS and parietal pleura photoevaporation using Thulium Cyber Laser™ (TCL) 150 W 2010 nm on the posterior third of three ribs; the pleural surface was homogeneously treated inside the target perimeter. The remaining ten pigs underwent uniportal thoracoscopy; talc poudrage was performed using the current clinical practice dosage (1 g/18 kg) with accurate talc powder spread over the whole pleural surface. All models were followed up for 60 days. Pleurodesis firmness was graded on a three-tier scale (none-moderate-firm) and site-matching topographical expectancy was evaluated. TCL produced pleurodesis in all models: 7/10 were firm and 3/10 moderate. Talc poudrage pleurodesis was firm in 4/10 and moderate in 6/10. Pleural adhesions were found exclusively in the treated area after laser treatment, while talc created a wide spectrum of effects, most commonly anarchic jagged adhesions obliterating less than 50 % of the pleural cavity (7/10), mostly declivous. The pathologist found more aggressive inflammation (sometimes severe) in the talc group. Expected localized pleurodesis was always registered in laser group (10/10), while talc poudrage was found poorly effective if consistent pleurodesis is expected in an apico-dorsal position (2/10). Laser pleurodesis appears more homogeneous, qualitatively not inferior, and topographically more predictable than talc pleurodesis. Parietal photoevaporation seems effective and the localized pleurodesis is reproducible.

Docetaxel rechallenge in metastatic castration-resistant prostate cancer: any place in the modern treatment scenario? An intention to treat evaluation.

BACKGROUND: We evaluated the possible advantages of a docetaxel (DCT) rechallenge strategy in metastatic castration-resistant prostate cancer (mCRPC) patients, also given the possible earlier positioning of this treatment option in the modern scenario. PATIENTS & METHODS: All mCRPC patients planned for DCT chemotherapy rechallenge in our institutions were evaluated. RESULTS: Of 128 patients, 98 achieved disease control on the initial DCT round. After a treatment holiday of 8.3 months, the 98 responsive patients underwent a second DCT round, with 56 cases achieving again disease control. After a 5.7-month off-treatment period, 32 of these cases underwent a third DCT round, and 16 responded. Lastly, after a further 4.2-month treatment holiday, eight patients underwent a fourth DCT round and two responded. Median time to definitive disease progression for the whole population was 16.4 months. CONCLUSIONS: Rechallenge with DCT may be considered a suitable treatment option for mCRPC patients recurring after a successful DCT chemotherapy. The interest in this strategy may be increased because of the showed efficacy of early DCT chemotherapy in patients with bulky disease (CHAARTED study) and the potential lower efficacy of the new hormonal agents abiraterone acetate and enzalutamide when used in a immediate sequencing.

Selumetinib: a promising pharmacologic approach for KRAS-mutant advanced non-small-cell lung cancer.

Selumetinib is a potent and selective inhibitor of MEK1 and 2 that is currently being clinically developed for the treatment of several human malignancies. Initially administered as free-base suspension, a more convenient Hyd-sulfate capsule formulation has recently been developed. Phase I studies revealed that acneiform dermatitis was the dose-limiting toxicity of both the free-base and capsule formulation given two-times a day at the maximum tolerated doses of 100 and 75 mg, respectively, with the capsule formulation resulting into a significantly higher drug bioavailability. Importantly, as a MEK inhibitor, selumetinib could be particularly effective in tumors with a hyperactivated Ras/Raf/MEK/ERK pathway, which might be the case of KRAS-mutant non-small-cell lung cancers (NSCLCs). Accordingly, a recent randomized Phase II study evaluating docetaxel plus selumetinib or placebo in KRAS-mutant pretreated advanced NSCLC patients has demonstrated a significant improvement in terms of response rate, progression-free survival and patient-reported outcomes in favor of the combination arm. These positive results support further clinical evaluation of selumetinib in NSCLC, and confirmatory ongoing and future trials will assess its role according to KRAS-mutation status and in combination regimens with other targeted agents.

Practice of Monitoring Cisplatin-Induced Ototoxicity by Audiology, ENT, and Oncology Specialists: A Survey-Based Study in a Single Italian Medical Center.

Ototoxic drugs can result in hearing loss and tinnitus. Early detection of the ototoxic process can help minimize or prevent these consequences. The American Speech-Language-Hearing Association has provided guidelines for monitoring ototoxicity, whereas Italy has not yet implemented a national monitoring protocol. This study aims to assess the current state of ototoxicity monitoring in patients receiving cisplatin therapy. A self-administered survey has been used to gather information from oncologists, audiologists, and ENT specialists. The research was conducted at Santa Maria della Misericordia hospital in Perugia. Two questionnaires were administered, one to ENT/audiology specialists and another to oncology specialists. Both questionnaires were used to collect information on awareness of chemotherapy-induced ototoxicity. A comprehensive understanding of cisplatin-induced ototoxicity has been widely established (100%). The most commonly reported audiological symptoms by patients were hearing loss (100%) and tinnitus (87.5%). The majority of ENT and audiologists (93.8%) and oncologists (92.9%) expressed the need for a specific ototoxic monitoring program. However, they noted the absence of a well-defined ototoxicity monitoring protocol. A well-established and efficient ototoxic monitoring system facilitates early detection of ototoxic hearing loss and subsequent rehabilitation of inevitable hearing impairment.

Preoperative or Perioperative Docetaxel, Oxaliplatin, and Capecitabine (GASTRODOC Regimen) in Patients with Locally-Advanced Resectable Gastric Cancer: A Randomized Phase-II Trial.

Docetaxel associated with oxaliplatin and 5-fluorouracil (FLOT) has been reported as the best perioperative treatment for gastric cancer. However, there is still some debate about the most appropriate number and timing of chemotherapy cycles. In this randomized multicenter phase II study, patients with resectable gastric cancer were staged through laparoscopy and peritoneal lavage cytology, and randomly assigned (1:1) to either four cycles of neoadjuvant chemotherapy (arm A) or two preoperative + two postoperative cycles of docetaxel, oxaliplatin, and capecitabine (DOC) chemotherapy (arm B). The primary endpoint was to assess the percentage of patients receiving all the planned preoperative or perioperative chemotherapeutic cycles. Ninety-one patients were enrolled between September 2010 and August 2016. The treatment was well tolerated in both arms. Thirty-three (71.7%) and 24 (53.3%) patients completed the planned cycles in arms A and B, respectively (p = 0.066), reporting an odds ratio for early interruption of treatment of 0.45 (95% confidence interval (CI): 0.18-1.07). Resection was curative in 39 (88.6%) arm A patients and 35 (83.3%) arm B patients. Five-year progression-free survival (PFS) was 51.2% (95% CI: 34.2-65.8) in arm A and 40.3% (95% CI: 28.9-55.2) in arm B (p = 0.300). Five-year survival was 58.5% (95% CI: 41.3-72.2) and 53.9% (95% CI: 35.5-69.3) (p = 0.883) in arms A and B, respectively. The planned treatment was more frequently completed and was more active, albeit not significantly, in the neoadjuvant arm than in the perioperative group.

Inappropriate doses of chemotherapy in Italian breast cancer patients enrolled in clinical trials.

AIMS AND BACKGROUND: The dose of delivered chemotherapy is important to evaluate the appropriateness of the anticancer treatment. This aspect has been scarcely studied in Italy. About 7 years ago, the Italian Group for Antiemetic Research (IGAR) published a large controlled study on the effectiveness of different antiemetic prophylaxis in patients submitted to moderately emetogenic chemotherapy, where the prescribed chemotherapy was recorded. The aim of our study was to evaluate the incidence of undertreatment and to detect clinical and nonclinical factors able to explain its variability. METHODS: An observational study on the IGAR databank was performed to evaluate the incidence of undertreatment in the prescription in conditions of clinical trial, where the doses belonged to the eligibility criteria, and to analyze the importance of clinical and nonclinical factors using multifactorial logistic models. RESULTS: 317 patients receiving cyclophosphamide, methotrexate, and fluorouracil (CMF) and 224 anthracycline-based chemotherapy were considered. In the CMF-treated patients, 22.4% received full doses, whereas in 53.6% all three drugs of the schedule were down-dosed. In the anthracycline-treated group, 38.6% and 3.4% of patients submitted to chemotherapy containing epirubicin and doxorubicin, respectively, were undertreated. Logistic models showed that undertreatment in CMF-treated patients depended significantly on the geographic area and setting of chemotherapy administration. Although not significant, differences between age class and Karnofsky performance status were also detected. In the epirubicin-treated group, all these factors were significant. CONCLUSIONS: The undertreatment of cancer patients is a relevant problem, because it could give, in daily clinical practice, worse results than those reported in clinical studies. Considering the setting of a clinical trial where our study was carried out, the incidence of undertreatment is surprisingly high. We do not know whether today, about 8 years after the IGAR study was carried out, the inappropriate dose of chemotherapy is still as frequent as we reported, but surely the topic deserves more attention.

Short-course versus split-course radiotherapy in metastatic spinal cord compression: results of a phase III, randomized, multicenter trial.

PURPOSE: Hypofractionated radiotherapy (RT) is often used in the treatment of metastatic spinal cord compression (MSCC). This randomized trial was planned to assess the clinical outcome and toxicity of two different hypofractionated RT regimens in MSCC. PATIENTS AND METHODS: Three hundred patients with MSCC were randomly assigned to a short-course RT (8 Gy x 2 days) or to a split-course RT (5 Gy x 3; 3 Gy x 5). Only patients with a short life expectancy entered the protocol. Median follow-up was 33 months (range, 4 to 61 months). RESULTS: A total of 276 (92%) patients were assessable; 142 (51%) treated with the short-course and 134 (49%) treated with the split-course RT regimen. There was no significant difference in response, duration of response, survival, or toxicity found between the two arms. When short- versus split-course regimens were compared, after RT 56% and 59% patients had back pain relief, 68% and 71% were able to walk, and 90% and 89% had good bladder function, respectively. Median survival was 4 months and median duration of improvement was 3.5 months for both arms. Toxicity was equally distributed between the two arms: grade 3 esophagitis or pharyngitis was registered in four patients (1.5%), grade 3 diarrhea occurred in four patients (1.5%), and grade 3 vomiting or nausea occurred in 10 patients (6%). Late toxicity was never recorded. CONCLUSION: Both hypofractionated RT schedules adopted were effective and had acceptable toxicity. However, considering the advantages of the short-course regimen in terms of patient convenience and machine time, it could become the RT regimen of choice in the clinical practice for MSCC patients.

Hyperthermic intraperitoneal chemotherapy as palliative treatment for malignant ascites A single-center experience and a review of the literature.

Malignant ascites is an abnormal accumulation of fluid in the peritoneal cavity of patients with intraperitoneal cancer dissemination. This clinical condition could represent the terminal evolution of a lethal disease and could influence the prognosis, severely impairing the patients' quality of life. Treatment options include a multitude of different procedures with limited efficacy and some degree of risk; diuretics, paracentesis, peritoneo-venous shunts and intraperitoneal biologic agents like anti-VEGF molecules, metalloproteinase inhibitors and immunomodulators are included. None of these approaches have been established as a standard of care because of their low efficacy or severe side effects. The last two decades saw the emergence of cytoreductive surgery with hyperthermic intraperitoneal perioperative chemotherapy (HIPEC) as a viable therapeutic approach resulting in an effective cure against refractory malignant ascites. The following describes our experiences with 3 cases together with a literature review. KEY WORDS: Chemotherapy, HIPEC, Laparoscopy, Malignant ascites.

Sacrum colon-rectal cancer metastasis: microwave ablation for palliative pain treatment.

Local treatment of bone metastasis (BM) remains controversial in colon-rectum carcinoma for pain control. A patient developed a sacrum BM 4years after a left colectomy for an adenocarcinoma. Metastasis was treated in one session of CT-guided microwave ablation showing good pain control immediately after and on follow-up at four months.

HER2 overexpression as a predictive marker in a randomized trial comparing adjuvant cyclophosphamide/methotrexate/5-fluorouracil with epirubicin in patients with stage I/II breast cancer: long-term results.

BACKGROUND: HER2 overexpression/amplification has been reported to be a predictor of prognosis in breast cancer and a potential marker for selecting the optimal adjuvant chemotherapy. PATIENTS AND METHODS: HER2 expression and its interaction with treatment were retrospectively evaluated in 266 of 348 patients in a trial comparing adjuvant CMF (cyclophosphamide/methotrexate/5-fluorouracil) with weekly epirubicin in stage I/II breast cancer. HER2 expression was determined by immunohistochemistry (IHC) using the monoclonal antibody CB11. Initially, any cell showing definite membrane staining was counted, and HER2 overexpression was analyzed as a continuous variable and as a dichotomous variable, with a cutoff of > 50% of positively stained cells. Subsequently, the same slides were reanalyzed with the HercepTest. RESULTS: Of the 266 tumors immunostained for HER2, 34% exhibited nearly homogeneous staining with > 50% positive cells. When the HercepTest was applied, 8% of tumors were IHC 3+ and 8% were IHC 2+. At 8 years, no statistically significant difference in relapse-free survival (RFS) and overall survival (OS) was observed between the treatment arms in patients with low versus high HER2 overexpression, although the number of events is low. The OS was statistically shorter in patients with high HER2 overexpression in the CMF arm, whereas no difference was observed in the epirubicin arm, suggesting that patients whose cancer overexpresses HER2 could benefit more from anthracycline-based therapy. CONCLUSION: HER2 overexpression was associated with a poorer OS but not a poorer RFS. However, a Cox regression model did not confirm the prognostic role of HER2 for OS.

Prognostic value of preoperative neutrophils to lymphocytes ratio in patients resected for gastric cancer.

BACKGROUND: The neutrophil/lymphocyte ratio (NLR) in the peripheral blood is considered an easily assessable prognostic factor in cancer patients. We evaluated the predictive significance of the NLR in patients affected by gastric cancer that underwent gastric resection. METHODS: From July 2003 to March 2012, 156 patients who had undergone gastrectomy with curative intent for gastric adenocarcinoma were included. Data were retrieved from a prospective collected database. NLR was calculated from lymphocyte and neutrophil counts on routine blood tests taken before surgery. Survival analyses were generated according to the Kaplan-Meier method. Univariate and multivariate analyses were carried out by the Cox proportional hazard model. RESULTS: The median follow-up time for surviving patients was 38 months (range 1 to 108 months) and median preoperative NLR was 2.3 (range .47 to 19.73). Subjects were dichotomized at the N/L value of 2.3. Median survival of patients with NLR below the median was around 60 months compared with the 36 months of patients with an NLR above the median. A multivariate analysis established a significant and independent relationship between the NLR and the overall survival with a P value of less than .05. CONCLUSIONS: The results suggest that the elevated preoperative NLR predicts poor overall survival following resection for gastric adenocarcinoma. It may be used as a simple, reliable prognostic factor for risk stratification.

Relevance of p53, bcl-2 and Rb expression on resistance to cisplatin-based chemotherapy in advanced non-small cell lung cancer.

PURPOSE: Tumors with p53 overexpression have been associated with enhanced resistance to cisplatin-based chemotherapy in a few and small studies involving non-small cell lung cancer. The relationships and interactions between p53, Rb and bcl-2 immunostaining, clinical parameters and response to cisplatin-based chemotherapy were evaluated in the present study. EXPERIMENTAL DESIGN: Histological specimens obtained by bronchial or fine-needle biopsy from patients who underwent cisplatin-based chemotherapy between 1992 and 1999 were evaluated by immunostaining. RESULTS: There were 102 patients, 88 men. Median age was 63 years; 47 had stage III and 55 stage IV disease. Forty-six tumor samples (45%) had positive immunostaining for p53, 61 (59%) had negative immunostaining for Rb and 8 (8%) had positive immunostaining for bcl-2. The response rate of the group with p53 positive immunostaining was 26% versus 57% of the p53 negative group (P=0.004). In multivariate analyses p53 positive immunostaining was identified as an independent predictive factor for resistance to cisplatin-based chemotherapy (P=0.006). CONCLUSIONS: Our study confirmed an association of p53 immunostaining and response rate of patients treated with cisplatin-based chemotherapy.

The clinical relevance of Bcl-2, Rb and p53 expression in advanced non-small cell lung cancer.

PURPOSE: The aim of this study was to evaluate the impact of Bcl-2, retinoblastoma (Rb) and p53 proteins on overall survival of 102 patients with locally advanced and metastatic NSCLC who underwent cisplatin-based chemotherapy. MATERIALS AND METHODS: Paraffin-embedded bronchial biopsy and fine-needle biopsy specimens were evaluated by an immunostaining method. RESULTS: Median age of analyzed patients was 61 years. Male/female ratio was 88/14. There were 10 (10%) patients with stage IIIA, 37 (36%) with stage IIIB and 55 (54%) with stage IV NSCLC. Only 15 (15%) tumor specimens had no detectable alterations for analyzed factors. Forty-six samples (45%) had positive immunostaining for p53, 61 (60%) had negative immunostaining for Rb and 8 (8%) had positive immunostaining for Bcl-2. Median and 5-year survival of analyzed population was 12 months and 6%, respectively. In univariate analysis Bcl-2 overexpression, stage (III versus IV) and normal lactate dehydrogenase (LDH) serum levels were associated with better overall survival (P<0.02, 0.001 and 0.03). In multivariate analysis, only stage was identified as an independent predictive factor. CONCLUSION: High frequency of Rb and Bcl-2 loss was detected in patients with advanced NSCLC. P53, Rb and Bcl-2 have not been shown to be independent predictors of survival even if Bcl-2 might have a particular relevance in patients with advanced NSCLC and should be better explored in this setting.

Long-term results of induction chemotherapy followed by concurrent chemotherapy and thoracic irradiation in limited small cell lung cancer.

BACKGROUND: Small cell lung cancer (SCLC) is a chemoresponsive tumor but overall survival remains poor even in limited disease (LD). With the aim of eradicating chemoresistant tumor cells and reducing toxicity, we investigated in this phase II trial the feasibility and outcome of a sequential approach of induction chemotherapy (CT) followed, in responding patients with LD-SCLC, by intensified platinum-based CT and concurrent thoracic irradiation (TI). MATERIALS AND METHODS: We treated 55 consecutive LD-SCLC patients with three 21-day cycles of cyclophosphamide, epiadriamycin and vincristine (CEV) as induction CT. In 44 (80%) patients there was an objective response and they received treatment intensification consisting of TI and concomitant CT with carboplatin and etoposide plus recombinant granulocite colony stimulating factor. Twenty-five (57%) patients were submitted to twice-daily thoracic irradiation (TDTI; 1.5 Gy per fraction, to a total dose of 45 Gy) and 19 (43%) to once-daily thoracic irradiation (ODTI; 2 Gy per fraction, to a total dose of 50 Gy). RESULTS: Median follow up was 75 months (range, 42-102). Of 44 patients submitted to intensification with TI plus CT, 32 (73%) had a complete and 12 (27%) a partial response. Median overall survival of all 55 patients was 17 months with actuarial survival probabilities of 2 and 5 years, 32 and 25%, respectively. Analysis of patient sub-groups showed a 5-month median survival in non-responders, 19 in TDTI and 17 in ODTI patients, respectively. Two and 5 year survival probabilities were 0% in non-responders, 40 and 35% in TDTI and 39 and 21% in ODTI patients, respectively. At present, 13 of 44 responders are still alive, of which nine (20%) have been progression-free from 45 to 93 months (median 60). Treatment failure was registered in 31 (70%) of 44 patients who received both induction and intensification treatment. One-half of patients had intrathoracic recurrence, eight of which only local and the remaining seven local and distant. Fourteen (32%) patients had brain metastases. Grade 3-4 neutropenia occurred in 24 (55%) patients with no differences between treatment groups. Grade 3 esophagitis was registered in four (9%) patients: in 3/25 (12%) and 1/19 (5%) of those who received TDTI and ODTI, respectively (P=not significant). Acute radiation pneumonitis occurred in three (12%) patients submitted to TDTI. No clinically debilitating pulmonary fibrosis, permanent esophageal stricture or toxic death was observed. CONCLUSIONS: In LD-SCLC patients late concurrent CT plus TI is feasible and effective. Our long-term results are similar to the best reported in the literature. Despite the high incidence of complete response obtained, however, one-half of the patients had intrathoracic relapse and one-third brain metastases.

Weekly paclitaxel in metastatic breast cancer patients: a phase II study.

UNLABELLED: AIMS ANID BACKGROUND: Paclitaxel, a microtubule inhibitor, is one of the most active drugs in metastatic breast cancer. A weekly schedule, at a median dose-intensity of 91 mg/m2, is effective and has less side effects than a 3-week schedule. In this phase II study, we evaluated the toxicity and the activity of weekly 1 hr paclitaxel infusions in metastatic breast cancer patients. STUDY DESIGN: Between February 1999 and February 2001, 26 patients with metastatic breast cancer were treated with weekly paclitaxel (60-90 mg/m2/1 hour iv infusion/weekly). The treatment was planned to continue until disease progression or prohibitive toxicity; in patients with responsive or stable disease, paclitaxel was stopped after 6 months of therapy. RESULTS: At a median follow-up of 18.7 months (range, 6.8-30.8), all patients are assessable for response and toxicity. We obtained 8 partial responses (30.8%), 8 stable disease (30.8%) and 10 disease progression (38.4.%). The overall response was 30.8% (95% CI, 13.1-48.5). The median duration of response was 7.6 months (range, 1.8-12.4); median time to progression was 4.86 months (range, 1.4-12.4); median overall survival was 9.9 months (range, 1.7-29.2+). Treatment was well tolerated. Hematological toxicity was mild and only one patient developed grade 3 anemia. Two patients experienced grade 3 cardiovascular toxicity; both had received anthracycline-based regimens. CONCLUSIONS: In our experience, weekly administration of paclitaxel shows a substantial degree of activity even in pretreated metastatic breast cancer patients. The toxicity profile is favorable.

T1-T2 breast cancer with four or more positive axillary lymph nodes: adjuvant locoregional radiotherapy with high-dose or standard-dose chemotherapy. Results of an observational study.

AIM AND BACKGROUND: The aim of this study was to investigate the efficacy of postoperative locoregional radiotherapy in patients with T1-T2 breast cancer and four or more positive axillary lymph nodes submitted to mastectomy or breast-conserving surgery followed by standard-dose or high-dose adjuvant chemotherapy. The incidence of locoregional relapses and the survival correlated with the number of positive nodes were recorded for each treatment arm. PATIENTS AND METHODS: From August 1992 to August 1999 86 breast cancer patients (median age, 54 years, T1-T2, N+ > or = 4) submitted to surgery were treated. Sixty-three patients received standard-dose chemotherapy while 23 patients with 10 or more positive nodes received high-dose chemotherapy. After four courses of standard-dose anthracycline-based chemotherapy peripheral blood stem cells were mobilized with cyclophosphamide (7 g/m2) and G-CSF (10-16 microg/kg/day/sc). High-dose chemotherapy consisted of etoposide 1000 mg/m2, thiotepa 500 mg/m2 and carboplatin 800 mg/m2. Hormone receptor-positive patients underwent hormone therapy. Following chemotherapy all 86 patients were given conventional radiotherapy to the breast or the chest wall and the supraclavicular fossa. The high-dose subgroup received radiotherapy to the internal mammary nodes +/- axilla. RESULTS: The median follow-up from the start of radiotherapy was 36.5 months. Locoregional relapses occurred in nine patients (10.4%); in four of them they were isolated (4.6%). Local relapses were four (4.6%) and regional relapses six (6.9%). Twenty-five patients (29%) had distant metastases. The five-year and eight-year overall actuarial survival rates were 82.6% +/- 4.8 and 60.1% +/- 8.8, respectively. No statistical differences were found when the number of positive nodes or the type of treatment of N+ 10 patients was included in the analysis. CONCLUSIONS: Breast cancer patients with four or more positive axillary lymph nodes are at high risk of developing locoregional and distant relapses. The results reported here demonstrate the efficacy of radiotherapy in the reduction of locoregional failure; no differences in survival and locoregional control in relation to treatment arm and number of positive nodes were found.

Prognostic factors in a multicentre study of 247 atypical pulmonary carcinoids.

OBJECTIVES: To analyse clinical and biomolecular prognostic factors associated with the surgical approach and the outcome of 247 patients affected by primary atypical carcinoids (ACs) of the lung in a multi-institutional experience. METHODS: We retrospectively evaluated clinical data and pathological tissue samples collected from 247 patients of 10 Thoracic Surgery Units from different geographical areas of our country. All patients were divided into four groups according to surgical procedure: sub-lobar resections (SURG1), lobar resections (SURG2), tracheobronchoplastic procedures (SURG3) and pneumonectomies (SURG4). Overall survival analysis was performed using the Kaplan-Meier method and log-rank test. Survival was calculated from the date of surgery to the last date of follow-up or death. The parameters evaluated included age, gender, smoking habits, laterality, type of surgery, 7th edition of TNM staging, mitosis Ki-67 (MIB1), multifocal forms, tumourlets, type of lymphadenectomy and neo/adjuvant therapy. For multivariate analysis, a Cox regression model was used with a forward stepwise selection of covariates. RESULTS: Two hundred and forty-seven patients (124 females and 123 males; range 10-84, median 60 years) underwent surgical resection for AC in the last 30 years as follows: n = 38 patients in SURG1, 181 in SURG2, 15 in SURG3 and 14 in SURG4. A smoking history was present in 136 of 247 (55%) patients. The median follow-up period was 98.7 (range 11.2-369.9) months. The overall survival probability analysis of the AC was 86.7% at 5 years, 72.4% at 10 years, 64.4% at 15 years and 58.1% at 20 years. Neuroendocrine multicentric forms were detected in 12 of 247 patients (4.8%; 1 of 12 pts) during the follow-up (range 11.2-200.4, median 98.7 months) and 33.4% had recurrence of disease. There were no significant differences between gender, tumour location and type of surgery at the multivariate analysis. Age [P < 0.001, hazard ratio (HR) 0.60; confidence interval (CI) 0.32-1.12], smoking habits (P = 0.002; HR 0.43, 95% CI 0.23-0.80) and lymph nodal metastatic involvement (P = 0.008; HR 0.46, 95% CI 0.26-0.82) were all significant at multivariate analysis. CONCLUSIONS: ACs of the lung are malignant neuroendocrine tumours with a worst outcome in patients over 70 years and in smokers. With the exception of pneumonectomy, the extent of resection does not seem to affect survival and should be accompanied preferably by lymphadenectomy. Pathological staging, along with a mitotic index more than Ki-67 (MIB1), appears to be the most significant prognostic factor at the univariate analysis.

Could interferon still play a role in metastatic renal cell carcinoma? A randomized study of two schedules of sorafenib plus interferon-alpha 2a (RAPSODY).

BACKGROUND: Sorafenib has proven efficacy in metastatic renal cell carcinoma (mRCC). Interferon (IFN) has antiangiogenic activity that is thought to be both dose- and administration-schedule dependent. OBJECTIVE: To compare two different schedules of IFN combined with sorafenib. DESIGN, SETTING, AND PARTICIPANTS: Single-stage, prospective, noncomparative, randomized, open-label, multicenter, phase 2 study on previously untreated patients with mRCC and Eastern Cooperative Oncology Group performance status 0-2. INTERVENTION: Sorafenib 400mg twice daily plus subcutaneous IFN, 9 million units (MU) three times a week (Arm A) or 3 MU five times a week (Arm B). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Primary end points were progression-free survival (PFS) for each arm and safety. Data were evaluated according to an intent-to-treat analysis. RESULTS AND LIMITATIONS: A total of 101 patients were evaluated. Median PFS was 7.9 mo in Arm A and 8.6 mo in Arm B (p=0.049) and the median duration of response was 8.5 and 19.2 mo, respectively (p=0.0013). Nine partial responses were observed in Arm A, and three complete and 14 partial responses were observed in Arm B (17.6% vs 34.0%; p=0.058); 24 and 21 patients (47% and 42%), respectively, achieved stable disease. The most common grade 3-4 toxicities were fatigue plus asthenia (28% vs 16%; p=0.32) and hand-foot skin reactions (20% vs 18%). CONCLUSIONS: Sorafenib plus frequent low-dose IFN showed good efficacy and tolerability. Further investigations should be warranted to identify a possible positioning of this intriguing regimen (6% complete response rate) in the treatment scenario of mRCC.

Diarrhoea in irradiated patients: a prospective multicentre observational study.

AIMS: To determine the incidence of cancer treatment-induced diarrhoea in patients submitted to irradiation. METHODS: Forty-five Italian radiation oncology departments took part in this prospective observational study and a total of 1020 patients were enrolled. The accrual lasted three consecutive weeks; evaluation was based on diary cards filled in daily by patients during radiotherapy and one week after cessation. Diary cards recorded both the onset and intensity of diarrhoea. RESULTS: A total of 1004 patients were eligible for this analysis. 147/1004 (14.6%) patients had diarrhoea. The median minimum number of daily events was 1 (range 1-7) with a median maximum events of 3 (range 1-23). 82/147 patients (56.2%) had a drug prescription for diarrhoea. In the evaluation of the onset of diarrhoea, in multivariate analysis, we found the following factors to be statistically significant predictors of an increased likelihood of diarrhoea: primitive tumour site, therapeutic purpose and field size. CONCLUSIONS: Patients with abdominal-pelvic cancer, treated with curative purpose and using large field sizes are at high risk of cancer treatment-induced diarrhoea. Diarrhoea was also observed in patients treated at other sites. In this population group there is the need for more stringent monitoring during the delivery of radiation therapy.