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BackgroundWeight loss in patients with metabolic syndrome has positive effects on cardiovascular and type 2 diabetes risks, but its effects on peripheral cytokines and lipid profiles in patients are still unclear.AimTo determine the effects of diet-induced weight loss on metabolic parameters, lipids and cytokine profiles.MethodsEighteen adult males with metabolic syndrome (defined according to IDF 2009) and Body Mass Index (BMI) between 25 and 35 kg/m2were subjected to a balanced hypocaloric diet for 6 months to reach at least a 5% body weight loss.ResultsAfter weight loss, a significant improvement in BMI, waist circumference, insulin, fasting blood glucose and HOMA-IR (homeostasis model assessment of insulin resistance) was observed. The analysis of LDL (low-density lipoprotein cholesterol) and HDL (high-density lipoprotein cholesterol) lipoproteins showed a change in their composition with a massive transfer of triacylglycerols from HDL to LDL. This was associated with a significant reduction in peripheral pro-inflammatory cytokines such as IL-6, TNF-α, IL-8 and MIP-1β, leading to an overall decreased inflammatory score. An interesting positive correlation was also observed among peripheral cytokines levels after diet and peripheral levels of CETP (cholesteryl ester transfer protein), an enzyme with a key role in lipid change.ConclusionWeight loss through caloric restriction is associated with an improvement in peripheral lipid and cytokine profiles that may play a major role in improving cardiovascular risk.Graphic abstract

A substantial proportion of patients who have recovered from coronavirus disease-2019 (COVID-19) experience COVID-19–related symptoms even months after hospital discharge. We extensively immunologically characterized patients who recovered from COVID-19. In these patients, T cells were exhausted, with increased PD-1+ T cells, as compared with healthy controls. Plasma levels of IL-1β, IL-1RA, and IL-8, among others, were also increased in patients who recovered from COVID-19. This altered immunophenotype was mirrored by a reduced ex vivo T cell response to both nonspecific and specific stimulation, revealing a dysfunctional status of T cells, including a poor response to SARS-CoV-2 antigens. Altered levels of plasma soluble PD-L1, as well as of PD1 promoter methylation and PD1-targeting miR–15-5p, in CD8+ T cells were also observed, suggesting abnormal function of the PD-1/PD-L1 immune checkpoint axis. Notably, ex vivo blockade of PD-1 nearly normalized the aforementioned immunophenotype and restored T cell function, reverting the observed post–COVID-19 immune abnormalities; indeed, we also noted an increased T cell–mediated response to SARS-CoV-2 peptides. Finally, in a neutralization assay, PD-1 blockade did not alter the ability of T cells to neutralize SARS-CoV-2 spike pseudotyped lentivirus infection. Immune checkpoint blockade ameliorates post–COVID-19 immune abnormalities and stimulates an anti–SARS-CoV-2 immune response.

Background: Survival after hospital admission has been evaluated as a possible risk factor for long-term mortality in selected classes of diseases. The aim of this study was to evaluate survival after hospital admission in all patients admitted as in-patients in a general hospital of Milano, Italy. Methods: 2,580 consecutive patients admitted at Ospedale San Paolo, July1-December 31, 2012, for several classes of diseases (internal medicine, cancer, infectious diseases, trauma and surgery, pneumonia, and heart diseases) were studied; age, total diseases, type of admission, length of admission, age-adjusted Charlson index, prognostic nutritional index (PNI), and full blood count were evaluated. Results: At univariate analysis, all investigated variables, except sex and lymphocytes, were associated with death of patients. At stepwise regression analysis, Charlson index or age plus total diseases, type of admission, number of admissions, and PNI were significant risk factors in the whole sample and in the majority of classes of diseases. Conclusion: Pre-existing conditions and nutritional state represent the major risk factor for mortality in most classes of disease, and possibly influence other predictors, such as type of admission, length of stay. This suggests that the current model of hospital admission might be improved, for instance through comprehensive care at home, instead of hospital admission, or before admission. Funding Information: This study received only institutional funds from Universita degli Studi di Milano and from IRCCS Multimedica; a grant by the Italian Ministry of Health (Ministero della Salute), was issued to IRCCS Multimedica (Ricerca Corrente). Declaration of Interests: LL, FG, ASZ, MF, AV, AEP, and ET declare no conflict of interest with the content of this paper. Ethics Approval Statement: The protocol of the study was approved by the local Ethics in 2013 (original study) and in 2020 (follow-up study).

OBJECTIVES: Pancoast tumour is a rare neoplasia in which the optimal therapeutic management is still controversial. The traditional treatment of Pancoast tumour (surgery, radiotherapy or a combination of both) have led to an unsatisfactory outcome due to the high rate of incomplete resection and the lack of local and systemic control. The aim of the study was to determine the efficacy of the trimodality approach. METHODS: Fifty-six patients (male/female ratio: 47/9, median age: 64 years) in stage IIB to IIIB were treated during a period between 1994 and 2013. Induction therapy consisted of 2-3 cycles of a platinum-based chemotherapy associated with radiotherapy (30–44 Gy). After restaging, eligible patients underwent surgery 2 to 4-week post-radiation. RESULTS: Thirty-two (57.1%) patients were cT3 and 24 (42.9%) cT4, 47 (83.9%) were N0 and 9 (16.1%) N+. Forty-eight (85.7%) patients underwent R0 resection and 10 (17.9%) had a complete pathological response (CPR). Thirty-day mortality rate was 5.4%, major surgical complications occurred in 6 (10.7%) patients. At the end of the follow-up, 17 (30.4%) patients were alive and 39 (69.6%) died (29 for cancer-related causes), with an overall 5-year survival of 38%. At statistical analysis, stage IIB (P= 0.003), R0 resection (P= 0.03), T3 tumour (P= 0.002) and CPR (P= 0.01) were significant independent predictors of better prognosis. CONCLUSIONS: This combined approach is feasible, and allows for a good rate of complete resection. Long-term survival rates are acceptable, especially for early stage tumours radically resected. Systemic control of disease still remains poor, with distant recurrence being the most common cause of death.

Background Low albumin levels and low lymphocyte counts are intra hospital conditions that exert a negative influence on prognosis, healing and length of hospitalization. The study aimed to analyze the correlation between low blood levels of albumin, low lymphocytes, and length of stay. The secondary aim was to identify other co-morbidities associated with prolonged hospital stay. Methods Retrospective pilot study was conducted by analyzing anamnestic and biochemical data, related to 4038 patients admitted to ten wards of Hospital San Paolo (Milan), collected from July 1st 2012 to December 31st 2012. A statistical analysis was carried out using the Correlation method, Multivariate Analysis and Regression. Lymphocyte count and co-morbidities were evaluated in the whole cohort, albumin levels in 1437 patients. Results In the whole sample, low albumin levels and low lymphocyte counts were directly correlated to longer hospitalizations. The stratification of the results by department and diagnosis suggests that there is a higher correlation in certain subpopulations, and albumin shows a greater correlation with length of stay than lymphocytes. Also advanced age, high platelets, type of diagnosis, male gender and emergency admission led to longer hospitalizations. Conclusions A routine check of albumin, lymphocytes and a spectrum of significant variables can provide precious information which can eventually lead to a shorter hospital stay. Knowledge of the general health status of a patient and the possibility to estimate his/her length of hospital stay are essential information for Clinical Governance, and for the improvement of internal services of hospitals on a large scale.

J Oral Pathol Med (2012) 41: 136–140 Background: There are currently no clinical or pathological parameters able to predict response to adjuvant radiotherapy (RT) in laryngeal squamous cell carcinoma (LSCC). Few studies have investigated the molecular pathways potentially capable of predicting said response. The mammalian target of rapamycin (mTOR) acts as a ‘master switch’ protein in cancer cells, modulating metabolism, the cell cycle, and apoptosis. Cancer treatment with mTOR inhibitors (rapamycin analogs, or rapalogs) has produced promising results in various malignancies (renal cell carcinoma, breast cancer, prostate cancer, leukemia, lymphoma, and melanoma). The novel aim of the present study was to ascertain the prognostic role of mTOR expression in a series of patients with LSCC treated with primary surgery followed by RT. Methods: The retrospective study involved 25 consecutive patients with LSCC given postoperative RT. Immunohistochemical mTOR expression was evaluated in primary LSCC by image analysis. Results: The locoregional recurrence rate was significantly higher in patients with LSCC whose mTOR expression was >2.5% (P = 0.013). After postoperative RT, the locoregional recurrence risk ratio was 3.25 in LSCCs with mTOR >2.5%. The different disease-free survival was significantly shorter in cases of LSCC with mTOR >2.5% (P = 0.029). Conclusions: mTOR should be studied as a potential predictor for identifying LSCCs at higher risk of early recurrence after postoperative RT. New therapeutic strategies should be investigated in LSCC, including the use of rapalogs associated with conventional chemotherapeutic regimens in combination with RT.

Background Chemo-radiotherapy is standard of care in the treatment of unresectable stage III NSCLC. We aimed at assessing whether the addition of concurrent taxane-chemotherapy to thoracic irradiation following chemotherapy was able to improve treatment outcome. Material and methods In PITCAP trial, patients with unresectable stage III NSCLC were randomized to receive 2 cycles of platinum-paclitaxel followed by 60–61.2Gy thoracic irradiation (control arm) or by same radiotherapy with concomitant weekly paclitaxel (experimental arm). A literature-based meta-analysis including all studies with same design was also performed. Results At the time of the second interim analysis, when 151 patients were randomized, accrual was terminated. With a median follow-up of 6.1 years, median survival was 13.2 vs 15.1 months, with a 3-year survival rate of 19.5 vs 21.2% in the control and experimental arm, respectively (HR: 0.97; 95% CI 0.69–1.36; p =0.845). Treatment toxicity was manageable in both arms. The meta-analysis of 5 trials (n=866) confirmed the lack of a meaningful effect on 1-year overall survival of a taxane added concurrently to radiotherapy. Conclusions These results do not support a meaningful survival benefit with the addition of single agent taxane given concurrently to radiotherapy after platinum-based induction in locally advanced NSCLC.

Trimodality therapy seems to be the best treatment for malignant pleural mesothelioma (MPM). A large experience served to evaluate the efficacy of surgery followed by adjuvant chemo-radiotherapy. Trimodality therapy results have led us to test induction chemotherapy followed by EPP and adjuvant radiotherapy in stages I-III of MPM. The aim of our study was to evaluate the feasibility of this protocol and to estimate survival.From 2000 to 2003, 21 patients with MPM (14 males and 7 females, median age 59 years) were enrolled in the prospective study. Induction chemotherapy consisted of Carboplatin (AUC 5mg/mL/min on Day 1) and Gemcitabine (1000mg/m(2) on Days 1, 8, 15) for three to four cycles. EPP was performed 3-5 weeks after induction therapy, while post-operative RT was given 4-6 weeks after operation.Ten patients received three cycles of chemotherapy, 10 patients received four cycles and 1 patient had two cycles. Grades 3-4 haematological toxicity occurred in eight (38.1%) patients. Chemotherapy response rate was: complete 0%, partial 33.3% and stable disease 66.7%. Seventeen (80.9%) out of 21 patients underwent EPP with no intra or post-operative mortality with an overall major and minor morbidity rate at 52.4%. Median survival was 25.5 months, with an overall 1, 3 and 5-year survival rate of 71, 33 and 19%, respectively.In MPM, the combined modality approach using the Carboplatin/Gemcitabine combination as induction chemotherapy is feasible, with good results in terms of survival and morbidity. Our results are similar to those of other studies using a heavier modality treatment.

Postoperative RT is generally recommended for laryngeal carcinomas (LSCCs) at high risk of recurrence after surgery. There are currently no clinicopathological parameters available to predict response to such adjuvant RT in LSCC, and only a few potentially predictive biomarkers have been investigated. Nm23-H1 protein is reportedly related to the tumor cells’ metastatic potential, and low Nm23-H1 expression levels in human carcinomas often correlate with a poor prognosis. The novel aim of the present preliminary study was to investigate the prognostic value of Nm23-H1 expression and subcellular localization in a series of patients given postoperative RT for LSCC. A retrospective clinicopathological investigation was conducted at an academic tertiary referral center of 28 consecutive patients given postoperative RT for LSCC. Image analysis of immunohistochemical reactions was performed to measure Nm23-H1 total and nuclear expression levels. Disease-free survival (DFS) was significantly shorter among LSCC patients with total Nm23-H1 levels

Laura Bonanno,1 Giulia Zago,1 Giuseppe Marulli,2 Paola Del Bianco,3 Marco Schiavon,2 Giulia Pasello,1 Valentina Polo,1,4 Fabio Canova,1 Fabrizio Tonetto,5 Lucio Loreggian,5 Federico Rea,2 PierFranco Conte,1,4 Adolfo Favaretto1 1Medical Oncology Unit 2, Veneto Institute of Oncology IOV-IRCCS, 2Thoracic Surgery Department, University of Padova, 3Clinical Trials and Biostatistics Unit, Veneto Institute of Oncology IOV-IRCCS, 4Department of Surgery, Oncology and Gastroenterology, University of Padova, 5Radiotherapy Unit, Veneto Institute of Oncology IOV-IRCCS, Padova, Italy Objectives: If concurrent chemoradiotherapy cannot be performed, induction chemotherapy followed by radical-intent surgical treatment is an acceptable option for non primarily resectable non-small-cell lung cancers (NSCLCs). No markers are available to predict which patients may benefit from local treatment after induction. This exploratory study aims to assess the feasibility and the activity of multimodality treatment, including triple-agent chemotherapy followed by radical surgery and/or radiotherapy in locally advanced NSCLCs. Methods: We retrospectively collected data from locally advanced NSCLCs treated with induction chemotherapy with carboplatin (area under the curve 6, d [day]1), paclitaxel (200 mg/m2, d1), and gemcitabine (1,000 mg/m2 d1, 8) for three to four courses, followed by radical surgery and/or radiotherapy. We analyzed radiological response and toxicity. Estimated progression-free survival (PFS) and overall survival (OS) were correlated to response, surgery, and clinical features. Results: In all, 58 NSCLCs were included in the study: 40 staged as IIIA, 18 as IIIB (according to TNM Classification of Malignant Tumors–7th edition staging system). A total of 36 (62%) patients achieved partial response (PR), and six (10%) progressions were recorded. Grade 3–4 hematological toxicity was observed in 36 (62%) cases. After chemotherapy, 37 (64%) patients underwent surgery followed by adjuvant radiotherapy, and two patients received radical-intent radiotherapy. The median PFS and OS were 11months and 23months, respectively. Both PFS and OS were significantly correlated to objective response (P

Patients with head and neck squamous cell carcinoma (SCC) respond very differently to radiotherapy (RT). Since clinical factors cannot accurately predict its effects, biological parameters have been investigated, including tumor hypoxia. CD105 is a hypoxia-inducible glycoprotein emerging as a potential prognostic indicator for several solid malignancies. Angiogenin is upregulated under hypoxic conditions and supports primary and metastatic tumor growth. Epidermal growth factor receptor (EGFR) activation stimulates tumor proliferation and angiogenesis. The aim of the present study was to ascertain the prognostic importance of hypoxia-inducible factors (CD105, angiogenin) and EGFR in a series of patients who underwent primary surgery followed by RT for laryngeal SCC. 25 consecutive patients with laryngeal SCC given postoperative RT have been investigated. CD105, angiogenin, and EGFR immunohistochemical expressions in primary laryngeal SCCs have been evaluated also with image analysis. The recurrence rate was significantly higher in SCC patients with a CD105 expression >10.0% (P = 0.012) and their disease-free survival (DFS) was shorter (P = 0.044). Neither angiogenin (in the carcinoma cells or endothelial cells) nor EGFR expression were associated with the prognosis in our patients after primary surgery followed by RT for laryngeal SCC. CD105 should be studied as a potentially predictive biomarker for identifying laryngeal SCCs at higher risk of early recurrence after postoperative RT. Targeted anti-CD105 therapy associated with RT should also be investigated in patients with laryngeal SCCs characterized by high CD105 expression.

Cisplatin and 5-fluorouracil act as radiosensitizers and are active cytotoxic drugs in head and neck cancer. Therefore, from May 1987 to June 1990, we gave a continuous course of radiotherapy (70 Gy/35 fractions/7 weeks) combined with the simultaneous administration, once a week, of cisplatin (40 mg/m2, i.v. bolus) and 5-fluorouracil (400 mg/m2, i.v. bolus) to 21 patients with locally advanced or recurrent tumors of the head and neck. The complete and partial response rates were 65% and 15%, respectively. With a median follow-up of 17 months (range: 4-42) and with 19/21 patients having stages III and IV tumors, 12 patients are NED (no evidence of disease), 8 died with tumor, and 1 died of bronchopneumonia during the treatment. The main toxicity was mucositis and the median length of therapy was higher than with irradiation alone. This regimen appears very encouraging and could be an improvement over radiation alone for patients with locally advanced head and neck cancer.

BACKGROUND: Concomitant chemoradiotherapy (CT/RT) is the standard treatment of locally advanced squamous cell carcinoma of the head and neck (SCCHN). We evaluated the efficacy of induction docetaxel (Taxotere), cisplatin, and 5-fluorouracil (TPF) before CT/RT versus CT/RT alone. PATIENTS AND METHODS: Patients with stage III-IVM0 SCCHN, Eastern Cooperative Oncology Group performance status of zero to one, were randomly assigned to receive CT/RT alone (arm A: two cycles of cisplatin 20 mg/m(2), days1-4, plus 5-fluorouracil 800 mg/m(2)/day 96 h continuous infusion, during weeks 1 and 6 of radiotherapy) or three cycles of TPF (arm B: docetaxel 75 mg/m(2) and cisplatin 80 mg/m(2), day 1, and 5-fluorouracil 800 mg/m(2)/day 96 h continuous infusion, every 3 weeks) followed by the same CT/RT. The primary end point was the rate of radiologic complete response (CR) at 6-8 weeks after the end of CT/RT. RESULTS: A total of 101 patients were randomly allocated to the study (51 arm A; 50 arm B). CR rates were 21.2% (arm A) versus 50% (arm B). Median progression-free survival and overall survival were, respectively, 19.7 and 33.3 months (arm A) and 30.4 and 39.6 months (arm B). Hematologic and non-hematologic toxic effects during CT/RT were similar in the two arms. CONCLUSION: Induction TPF followed by CT/RT was associated with higher radiologic CR in patients with locally advanced SCCHN with no negative impact on CT/RT feasibility.

In 1986, we initiated a multicenter, randomized trial to compare induction chemotherapy with cisplatin and 5-fluorouracil followed by locoregional treatment (surgery and radiotherapy or radiotherapy alone) with locoregional treatment alone in patients with head and neck squamous cell carcinoma. Here we report the long-term results of the trial. A total of 237 patients with nonmetastatic stage III or IV head and neck carcinoma were randomly assigned to receive four cycles of neoadjuvant chemotherapy followed by locoregional treatment (group A) or locoregional treatment alone (group B). Among all patients, overall survival at 5 and 10 years was 23% (95% confidence interval [CI] = 15.3% to 30.9%) and 19% (95% CI = 11.6% to 26.4%), respectively, for those in group A and 16% (95% CI = 9.6% to 23.4%) and 9% (95% CI = 3.5% to 14.7%), respectively, for those in group B (P = .13). Among operable patients, we observed no difference between group A and group B in overall survival at 5 and 10 years (group A, 31% [95% CI = 14.9% to 47.3%] and 22.7% [95% CI = 7.1% to 38.3%], respectively; group B, 43.3% [95% CI = 25.6% to 61.0%] and 14.2% [95% CI = 0.1% to 28.3%], respectively; P = .73). Among inoperable patients, overall survival at 5 and 10 years was 21% (95% CI = 12.3% to 30.1%) and 16% (95% CI = 7.7% to 23.9%), respectively, for group A and 8% (95% CI = 1.5% to 12.3%) and 6% (95% CI = 0.1% to 9.1%), respectively, for group B (log-rank P = .04). Four cycles of neoadjuvant chemotherapy is a promising approach for treating patients with inoperable advanced head and neck cancer but not for treating patients with operable disease.

Aim: Locally advanced NSCLCs are not primarily resectable due to local invasion of vital structure or to the degree of nodal involvement. Intensive chemotherapy induction treatment could improve the response rate and potentially the rate of patients able to undergo radical intent local treatment. The present study aims to assess the response rate and the feasibility of induction chemotherapy with carboplatin, paclitaxel and gemcitabine followed by surgery and postoperative radiotherapy. Methods: We retrospectively collected clinical data and radiological imaging from locally-advanced NSCLCs treated with carboplatin (AUC 6 d1), paclitaxel (200 mg/m2, d 1) and gemcitabine (1000 mg/m2 d1,8) for 3/4 courses, followed by surgery and/or radical intent radiotherapy. We analyzed the radiological response to chemotherapy according to RECIST v1.1 criteria as primary end-point. We collected the data about toxicity. Median Progression-free survival (PFS) and Overall survival (OS) of the study population have been estimated and correlated to radiological response, surgery and clinical features. Results: 58 locally advanced NSCLCs were included in the study: 41 were radiologically staged as stage IIIA, 17 as stage III B according to the 7th TNM classification. After chemotherapy, 37 (64%) patients underwent surgery followed by adjuvant radiotherapy, one patient received radical intent radiotherapy. Median delayed time to surgery was 2 weeks. Partial response was observed in 36 (62%, 95%CI: 48%-74%) cases, progression in 6 (10%) cases. 36 (62%) patients experienced grade 3-4 hematological toxicity. Main non hematological toxicities were grade 1-2 nausea and arthralgia. One patient was hospitalized for febrile neutropenia. The median PFS and OS of the study population were 10 and 26 months respectively. One-year PFS and OS rate were 44% and 76%. Objective response and surgery were significantly associated both with PFS (p Conclusions: The intensive chemotherapy induction treatment was feasible and associated with a considerable radiological response rate. We are planning prospective validation of the proposed multimodality treatment. Disclosure: All authors have declared no conflicts of interest.

Despite the reduction in the incidence of brain metastases following prophylactic cranial irradiation (PCI) in patients with small-cell lung cancer (SCLC), the use of this modality is still controversial due to the lack of improvement in survival and the appearance of neurotoxicity in long-term survivors. Moreover, the optimum dose, fraction size, and timing are not known. From 1980 to 1988, 70 patients with limited stage SCLC underwent PCI after or during multimodality treatment of their primary tumor. Most of these patients (75.7%) received an unconventional ultrarapid high-dose course of 17 Gy in two fractions over 3 days. Long-term (range 60-138 months) survivors (n = 16) were invited to have a complete neurological evaluation including computed cranial tomography (CCT), 99mTc-HMPAO single photon emission computerized tomography (SPECT) scan, electroencephalography (EEG), magnetic resonance imaging (MRI), and neuropsychometry. Delayed neurologic complications or psychometric impairment was observed in 46% of patients. One or more abnormalities were detected by CCT in all patients, and the presence of neurologic complications seemed to correlate with periventricular and subcortical white matter changes. A strong correlation was found between CCT and SPECT periventricular white matter changes. Although the incidence of late neurologic toxicity following this rapid course of irradiation was high, clinical findings were less severe than expected, and all the patients were capable of self-care.

Head and neck cancer is quite common in the elderly, its most common origin being the larynx, oropharynx and oral cavity. In patients aged 70 and over, assessment of comorbidity and performance status is very important in order to establish the most suitable therapeutic approach, if feasible. Often radiation therapy is the only choice because the patient general condition may entail an excessively high risk for surgery. In the literature there are scarce studies focusing on radiation therapy and its complications, and only retrospective data are available: for this reason the Italian "Geriatric Radiation Oncology Group" (GROG) has planned a prospective study in order to collect the different results achieved in head and neck cancer treated in the same period with radiation therapy, or surgery or both.

The aim of this study was to evaluate the feasibility, the response rate and the effect on survival of full dose polychemotherapy delivered concurrently with bifractionated radiotherapy at a radical dose, in a subset of patients with marginally resectable or unresectable stage IIIA-B non-small cell lung cancer (NSCLC). Treatment consisted of two courses of cisplatin 100 mg/m 2 for 1 day plus etoposide 120 mg/m 2 for 3 days delivered from day 1 to day 22, plus radiotherapy delivered in two cycles of 2560 cGy each from day 3 to day 12 and from day 24 to 33 (total dose 5120 cGy in 31 days). The daily dose was 320 cGy in two equal fractions. After surgery, three additional courses of cisplatin plus etoposide were planned. From February 1988 to June 1991, 39 patients with stage III NSCLC (19 were judged as having marginally resectable, 20 as having unresectable disease) were entered into the study. Out of 39 patients (22 squamous cell carcinoma, 17 adeno/large cell carcinoma), 24 had stage IlIa (62%) and 15 stage IIIb (38%). Median PS was 80 (70–90). A total of 78 (74 evaluable) concurrent cycles of pre-operative chemoradiotherapy were delivered. The prominent side-effect was leucopenia: leucopenia ≥grade 3 at nadir occurred in 20 cycles (27%), thrombocytopenia >- grade 3 at nadir in seven cycles (9%). 19 patients (54%) had a treatment delay of 1 week between the two cycles. Other important toxicities were sepsis in 5 patients (13%), oesophagitis > grade 2 in 9 patients (23%) and pneumonitis in 5 patients (13%). The response rate was 67% (6 CR (complete response), 16%; 19 PR (partial response), 51%). A resection was subsequently performed in 20 (51%) patients: 14 out of 19 marginally resectable (74%) and 6 out 20 initially unresectable (30%) patients. One other patient had an exploratory thoracotomy. Surgical specimens were tumour-free in 3 patients (14%); in 8 patients (38%) only microscopic tumour was found, and in 10 (48%) macroscopic residual tumour was found. Out of 23 patients attaining a CR, 5 relapsed locally and 11 only distantly. At present, with a follow-up ranging from 64 to 90 months, 34 patients have died, 1 is alive with recurrent disease and 4 (17%) are alive without evidence of disease. Median survival was 16 months, with 18% 3-year survivors and 13% 5-year survivors. Resected patients had a median survival of 21 months, versus 10 months for unresected patients ( P = 0.01). No significant difference was evident between stage IIIa and stage IIIb patients.

According to current literature, the main cause of death in patients with gallbladder (GB) and extrahepatic biliary ducts (EHBD) neoplasms is related to local and locoregional tumor spread rather than to distant metastases. Surgery, even when radical, is followed by a high number of relapses. That is why postoperative radiation therapy (RT) is usually combined with surgery. Alone, however, RT is not effective enough to markedly improve loco-regional control, considering that the adjacent organs would be damaged by higher doses. Referring to experimental studies published in the 1960s and relative to the biological effect of ionizing radiation with 5-Fluorouracil (5-FU) in slowing the pace of tumor growth, the Department of Radiotherapy, together with the Department of Medical Oncology in Padua General Hospital, began administering a combined surgical-chemo-radiotherapeutic protocol in January 1982, to January 1989. The protocol included 5-FU administration both 3 days before and during RT, after a surgical intervention as radical as possible. Eighteen patients were given this treatment. By the end of December 1989, 7 patients were alive--6 of them disease-free with a 26-month mean survival. Eleven patients died--7 due to local/loco-regional relapse, 1 from a distant metastasis, 1 from gastric hemorrhage, with no disease, and 2 from unknown causes. Overall mean survival in the two groups was 16 months. The combined treatment proved to be tolerable and feasible, even though severe complications were observed in 2 patients, 1 case of toxic death (gastric hemorrhage) and another with complete duodenal stenosis which required further surgery.(ABSTRACT TRUNCATED AT 250 WORDS)

7578 Background: SST is an uncommon neoplasia, whose optimal treatment remains controversial. Recently preoperative chemo- radiotherapy is arousing interest. Methods: Treatment consisted of a plati...

5518 Background: Concomitant CT/RT is the standard treatment for LASCCHN. Induction chemotherapy followed by CT/RT vs CT/RT alone have not yet been compared. The feasibility of TPF followed by CT/RT has been evaluated in a previous study (Int J Rad Oncol Biol Phys 2004, 59:481). Methods: Pts with inoperable stage III-IVa, PS 0–1, were randomized to CT/RT [2 cycles of Cisplatin 20 mg/sqm days 1–4, 5FU 800 mg/sqm 96 hours c.i. weeks 1 and 6 during RT (66–70 Gy)] (Arm A) or 3 cycles of neoadjuvant TPF (Docetaxel 75mg/sqm day1, Cisplatin 80mg/sqm day1, 5FU 800mg/sqm 96 hours c.i) followed by the same CT/RT (Arm B). Pts were stratified according to tumor site, T stage and nodal status. Neck dissection was performed in N2-N3 patients with pathological CR on primary tumor. The planned sample size was 96 pts to detect a difference in CR (primary endpoint) up to 15% in favour of arm B. The radiological responses were evaluated by an internal committee according to RECIST criteria. Results: Preliminary data are available for 84/96 randomized pts (42 arm A, 42 arm B). Pts/tumor characteristics are well balanced in the two arms. Toxicities during induction TPF consisted primarily of G3–4 granulocytopenia 56% (febrile neutropenia: 7.5%). Grade 3–4 toxicities during CT/RT in arm A and B were mucositis (42% and 26%), dysphagia (20% and 9%), skin reaction (12% and 8.6%), asthenia (5% and 3%); G3 weight loss (2% and 3%), G3 dry-mouth (0% and 3%). Duration of CT/RT was equivalent: 6.1 wks (4.2–8.7) in arm A and 6.3 wks (3.8–9.5) in arm B. At the end of CT/RT, in the 82 pts evaluable for efficacy, radiological CR were 20% (95% CI 8–37%) in arm A and 64% (95% CI 45–80%) in arm B. Conclusions: Three cycles of neoadjuvant TPF are feasible and don’t compromise subsequent concomitant CT/RT with comparable toxicity pattern. At the end of the treatment sequence serious adverse events were 31% in arm A and 34% in arm B. The difference in CR of 40% in favour of arm B justifies the following phase III study. Final results including pCR and DFS will be presented at the meeting. [Table: see text]

5532 Background: In 1986, the Gruppo di Studio sui Tumori Testa e Collo (GSTTC) started a multicenter randomized trial comparing induction CT with Cisplatin and 5Fluorouracil 120h c.i. (PF) followed by locoregional treatment (Surgery+RT or RT alone) (Group A) versus locoregional therapy (LRT) alone (Group B) in resectable or unresectable stage III-IVM0 H&N Squamous Cell Carcinoma. Our previous report (J Natl Cancer Inst 86: 265–72,1994), showed that 4 cycles of PF before LRT improved local control, decreased the incidence of distant metastases and increased Disease-Free-Survival (DFS) and Overall Survival (OS) in the subgroup of inoperable patients. Methods: From March 1986 to February 1990, 237 patients with stage III-IVM0 were randomized to 4 neoadjuvant PF followed by LRT or LRT alone. After a minimum follow-up of 10 years, the two treatments were compared in univariate and multivariate analysis for OS. Results: Of the 237 patients, 118 group A and 119 group B, 92% and 90% respectively were male, 25% a...

The authors examine 62 cases of curietherapy in the deep vagina on 21 cases of utero-vaginal applications and make a comparison between two dosimetric methods used to measure the dose to the rectum and to the bladder: the direct measure by the Siemens Gammameter dosimeter and the Chassagne-Horiot method. Very large differences were found between the doses evaluated by the two methods. The values with the direct measure were often found to be higher than the calculated ones. When the measurements were done by different doctors, the result was almost the same.