El papel del antígeno prostático específico (PSA) y el estadio patológico antes de la radioterapia en la predicción de los resultados de la resonancia magnética multiparamétrica (RMmp) en pacientes con recidiva del cancer de próstata tras prostatectomía radical / Role of PSA levels and pathological stadiation before radiation therapy in predicting mp-MRI results in patients with prostate cancer recurrence after radical prostatectomy

Objetivo Evaluar el valor del antígeno prostático específico (PSA) en la predicción de los resultados de la resonancia magnética multiparamétrica (RMmp) en pacientes con cáncer de próstata (CaP) de alto (puntuación de Gleason≥8, pT≥3, pN1) y bajo grado (puntuación de Gleason<8, pT<3, pN0). Materiales y métodos Ciento ochenta y ocho pacientes se sometieron a una RMmp de 1,5-T después de la prostatectomía radical y antes de la radioterapia. Los pacientes se dividieron en 2 grupos: el grupo A incluía pacientes con recidiva bioquímica (RB) y el grupo B pacientes sin RB pero con alto riesgo de recidiva local. Teniendo en cuenta la puntuación de Gleason, pT y pN como variables de agrupación independientes, se realizaron análisis ROC de los niveles de PSA en el momento del diagnóstico del CaP primario y antes de la radioterapia con el fin de identificar el punto de corte óptimo para predecir el resultado de la RMmp. Resultados En los grupos A y B, el área bajo la curva del PSA antes de la radioterapia fue superior a la del PSA en el momento del diagnóstico del CaP, en tumores de bajo y alto grado. Para los tumores de bajo grado, la mejor área bajo la curva fue de 0,646 y 0,685 en el grupo A y B, respectivamente; para los tumores de alto grado, la mejor área bajo la curva fue de 0,705 y 1 en el grupo A y B, respectivamente. Para los tumores de bajo grado, el punto de corte óptimo del PSA fue de 0,565-0,58ng/ml en el grupo A (sensibilidad y especificidad: 70,5% y 66%), y de 0,11-0,13ng/ml en el B (sensibilidad y especificidad: 62,5% y 84,6%). Para los tumores de alto grado, el punto de corte de PSA óptimo fue de 0,265-0,305ng/ml en el grupo A (sensibilidad y especificidad: 95% y 42,1%), y de 0,13-0,15ng/ml en el grupo B (sensibilidad y especificidad: 100%). Conclusión La RMmp se debe realizar como herramienta diagnóstica complementaria siempre que se detecte una RB, especialmente en el CaP de alto grado... (AU)

Objective To evaluate prostate-specific antigen (PSA) value in multiparametric magnetic resonance imagin (mp-MRI) results prediction, analyzing patients with high (Gleason Score ≥8, pT≥3, pN1) and low grade (Gleason Score <8, pT<3, pN0) prostate cancer (PCa). Materials and methods One hundred eighty-eight patients underwent 1.5-T mp-MRI after radical prostatectomy and before radiotherapy. They were divided into 2 groups: A and B, for patients with biochemical recurrence (BCR) and without BCR but with high local recurrence risk. Considering Gleason Score, pT and pN as independent grouping variables, ROC analyses of PSA levels at primary PCa diagnosis and PSA before radiotherapy were performed in order to identify the optimal cut-off to predict mp-MRI result. Results Group A and B showed higher area under the curve for PSA before radiotherapy than PSA at PCa diagnosis, in low and high grade tumors. For low grade tumors the best area under the curve was 0.646 and 0.685 in group A and B; for high grade the best area under the curve was 0.705 and 1 in group A and B, respectively. For low grade tumors the best PSA cut-off was 0.565-0.58ng/ml in group A (sensitivity, specificity: 70.5%, 66%), and 0.11-0.13ng/ml in B (sensitivity, specificity: 62.5%, 84.6%). For high grade tumors, the best PSA cut-off obtained was 0.265-0.305ng/ml in group A (sensitivity, specificity: 95%, 42.1%), and 0.13-0.15ng/ml in B (sensitivity, specificity: 100%). Conclusion Mp-MRI should be performed as added diagnostic tool always when a BCR is detected, especially in high grade PCa. In patients without BCR, mp-MRI results, although poorly related to pathological stadiation, still have a good diagnostic performance, mostly when PSA>0.1-0.15ng/ml. (AU)

Role of psa levels and pathological stadiation before radiation therapy in predicting mp-MRI results in patients with prostate cancer recurrence after radical prostatectomy.

OBJECTIVE: To evaluate PSA value in mp-MRI results prediction, analyzing patients with high (GS≥8, pT≥3, pN1) and low grade (GS<8, pT<3, pN0) Prostate Cancer (PCa). MATERIALS AND METHODS: One hundred eighty-eight patients underwent 1.5-Tmp-MRI after Radical Prostatectomy (RP) and before Radiotherapy (RT). They were divided into 2 groups: A and B, for patients with biochemical recurrence (BCR) and without BCR but with high local recurrence risk. Considering Gleason Score (GS), pT and pN as independent grouping variables, ROC analyses of PSA levels at primary PCa diagnosis and PSA before RT were performed in order to identify the optimal cut-off to predict mp-MRI result. RESULTS: Group A and B showed higher AUC for PSA before RT than PSA at PCa diagnosis, in low and high grade tumors. For low grade tumors the best AUC was 0.646 and 0.685 in group A and B; for high grade the best AUC was 0.705 and 1 in group A and B, respectively. For low grade tumors the best PSA cut-off was 0.565-0.58ng/mL in group A (sensitivity, specificity: 70.5%, 66%), and 0.11-0.13ng/mL in B (sensitivity, specificity: 62.5%, 84.6%). For high grade tumors, the best PSA cut-off obtained was 0.265-0.305ng/mL in group A (sensitivity, specificity: 95%, 42.1%), and 0.13-0.15ng/mL in B (sensitivity, specificity: 100%). CONCLUSION: Mp-MRI should be performed as added diagnostic tool always when a BCR is detected, especially in high grade PCa. In patients without BCR, mp-MRI results, although poorly related to pathological stadiation, still have a good diagnostic performance, mostly when PSA>0.1-0.15ng/mL.

El papel de la resonancia magnética multiparamétrica en el diagnóstico de la recidiva local tras la prostatectomía radical y antes de la radioterapia de rescate / The role of multiparametric magnetic resonance imaging in the diagnosis of local recurrence after radical prostatectomy and before salvage radiotherapy

Objetivo Evaluar la precisión diagnóstica de la resonancia magnética multiparamétrica (RMmp) en la detección de la recidiva local del cáncer de próstata (CaP) después de la prostatectomía radical (PR) y antes de la radioterapia (RT). Materiales y métodos Un total de 188 pacientes se sometieron a una RMmp de 1,5T después de la PR y antes de la RT. Los pacientes se dividieron en 2 grupos: con recidiva bioquímica (grupo A) y sin recidiva bioquímica, pero con alto riesgo de recidiva local (grupo B). Las variables continuas se compararon entre los 2 grupos mediante la prueba t de Student; las variables categóricas se analizaron mediante chi-cuadrado de Pearson. El análisis ROC se realizó considerando como variables de agrupación el PSA antes de la RT, el grado ISUP, el pT y el pN. Resultados La recidiva del CaP (reducción de los niveles de PSA después de la RT) fue del 89,8% en el grupo A y del 80,3% en el grupo B. Al comparar los pacientes con y sin recidiva del CaP, hubo una diferencia significativa en los valores de PSA antes de la RT para el grupo A, y en los valores de PSA antes y después de la RT para el grupo B. En el grupo A hubo una correlación significativa entre el PSA antes de la RT y el diámetro de la recidiva, y entre el PSA antes de la RT y el tiempo transcurrido hasta la recidiva. La precisión diagnóstica de la RMmp en la detección de la recidiva local del CaP tras la RT es del 62,2% en el grupo A y del 38% en el grupo B. La imagen potenciada en difusión es la secuencia de RM más específica y la perfusión dinámica con contraste la más sensible. Para el PSA=0,5ng/ml, el AUC disminuye, mientras que la sensibilidad y la precisión aumentan para cada secuencia de RM. Para el PSA=0,9ng/ml, el AUC de la perfusión dinámica con contraste aumenta significativamente (AU)

Purpose Assess multiparametric-MRI (mp-MRI) diagnostic accuracy in the detection of local recurrence of prostate cancer (PCa) after radical prostatectomy (PR) and before radiation therapy (RT). Materials and methods A total of 188 patients underwent 1.5-T mp-MRI after RP before RT. Patients were divided into 2 groups: with biochemical recurrence (group A) and without but with high risk of local recurrence (group B). Continuous variables were compared between 2 groups using Student-t test; categoric variables were analyzed using Pearson chi-square. ROC analysis was performed considering PSA before RT, ISUP, pT and pN as grouping variables. Results PCa recurrence (reduction of PSA levels after RT) was 89.8% in group A and 80.3% in group B. Comparing patients with and without PCa recurrence, there was a significant difference in PSA values before RT for group A and for PSA values before RT and after RT for group B. In group A, there was a significant correlation between PSA before RT and diameter of recurrence and between PSA before RT and time spent before recurrence. The mp-MRI diagnostic accuracy in detecting PCa local recurrence after RP is of 62.2% in group A and 38% in group B. Diffusion weighted imaging is the most specific MRI-sequence and dynamic contrast enhanced the most sensitive. For PSA=0.5ng/ml, the AUC decreases while sensitivity and accuracy increase for each MRI-sequence. For PSA=0.9ng/ml, dynamic contrast enhanced-AUC increases significantly. Conclusion mp-MRI should always be performed before RT when a recurrence is suspected. New scenarios can be opened considering the role of diffusion weighted imaging for PSA≤0.5ng/ml (AU)

The role of multiparametric mri in the diagnosis of local recurrence after radical prostatectomy and before salvage radiotherapy.

PURPOSE: Assess multiparametric-MRI (mp-MRI) diagnostic accuracy in the detection of local recurrence of Prostate Cancer (PCa) after Radical Prostatectomy (PR) and before Radiation Therapy (RT). MATERIALS AND METHODS: A total of 188 patients underwent 1.5-T mp-MRI after RP before RT. Patients were divided into two groups: with biochemical recurrence (group A) and without but with high risk of local recurrence (group B). Continuous variables were compared between two groups using T-Student; categoric variables were analyzed using Pearson chi-square. ROC analysis was performed considering PSA before RT, ISUP, pT and pN as grouping variables. RESULTS: PCa recurrence (reduction of PSA levels after RT) was 89.8% in the group A and 80.3% in the group B. Comparing patients with and without PCa recurrence, there was a significant difference in PSA values before RT for group A and for PSA values before RT and after RT for group B. In group A, there was a significant correlation between PSA before RT and diameter of recurrence and between PSA before RT and time spent before recurrence. The mp-MRI diagnostic accuracy in detecting PCa local recurrence after RP is of 62.2% in group A and 38% in group B. DWI is the most specific MRI-sequence and DCE the most sensitive. For PSA = 0.5 ng/ml, the AUC decreases while sensitivity and accuracy increase for each MRI-sequence. For PSA = 0.9 ng/ml, DCE-AUC increases significantly. CONCLUSION: mp-MRI should always be performed before RT when a recurrence is suspected. New scenarios can be opened considering the role of DWI for PSA ≤ 0.5 ng/ml.

Postoperative radiotherapy after upfront radical prostatectomy: debated issues at a turning point-a survey exploring management trends on behalf of AIRO (Italian Association of Radiotherapy and Clinical Oncology)

Objectives Postoperative prostate cancer patients are a heterogeneous population, and many prognostic factors (e.g., local staging, PSA kinetics, margin status, histopathological features) may influence their clinical management. In this complex scenario, univocal recommendations are often lacking. For these reasons, the present survey was developed by the Italian Association of Radiotherapy and Clinical Oncology (AIRO) to collect the opinion of Italian radiation oncologists and delineate a representation of current clinical practice in our country. Methods A questionnaire was administered online to AIRO (Italian Association of Radiotherapy and Clinical Oncology) members registered in 2020 with a clinical interest in uro-oncological disease. Results Sixty-one per cent of AIRO members answered the proposed survey. Explored topics included career and expertise, indications to adjuvant RT, additional imaging in biochemical recurrence setting, use of salvage radiotherapy (SRT), management of clinically evident locoregional recurrence and future considerations. Conclusions Overall, good level of agreement was found between participants for most of the topics. Most debated issues regarded, as expected, implementation of new imaging methods in this setting. Notably, trend in favour of early SRT vs. immediate adjuvant RT was underlined, and preference for global evaluation rather than isolated risk factors for RT indications was noticed (AU)

Postoperative radiotherapy after upfront radical prostatectomy: debated issues at a turning point-a survey exploring management trends on behalf of AIRO (Italian Association of Radiotherapy and Clinical Oncology).

OBJECTIVES: Postoperative prostate cancer patients are a heterogeneous population, and many prognostic factors (e.g., local staging, PSA kinetics, margin status, histopathological features) may influence their clinical management. In this complex scenario, univocal recommendations are often lacking. For these reasons, the present survey was developed by the Italian Association of Radiotherapy and Clinical Oncology (AIRO) to collect the opinion of Italian radiation oncologists and delineate a representation of current clinical practice in our country. METHODS: A questionnaire was administered online to AIRO (Italian Association of Radiotherapy and Clinical Oncology) members registered in 2020 with a clinical interest in uro-oncological disease. RESULTS: Sixty-one per cent of AIRO members answered the proposed survey. Explored topics included career and expertise, indications to adjuvant RT, additional imaging in biochemical recurrence setting, use of salvage radiotherapy (SRT), management of clinically evident locoregional recurrence and future considerations. CONCLUSIONS: Overall, good level of agreement was found between participants for most of the topics. Most debated issues regarded, as expected, implementation of new imaging methods in this setting. Notably, trend in favour of early SRT vs. immediate adjuvant RT was underlined, and preference for global evaluation rather than isolated risk factors for RT indications was noticed.

The Third Italian Consensus Conference for Malignant Pleural Mesothelioma: State of the art and recommendations.

Malignant Pleural Mesothelioma (MPM) remains a relevant public health issue, and asbestos exposure is the most relevant risk factor. The incidence has considerably and constantly increased over the past two decades in the industrialized countries and is expected to peak in 2020-2025. In Italy, a standardized-rate incidence in 2011 among men was 3.5 and 1.25 per 100,000 in men and women, respectively, and wide differences are noted among different geographic areas. The disease remains challenging in terms of diagnosis, staging and treatment and an optimal strategy has not yet been clearly defined. The Third Italian Multidisciplinary Consensus Conference on Malignant Pleural Mesothelioma was held in Bari (Italy) in January 30-31, 2015. This Consensus has provided updated recommendations on the MPM management for health institutions, clinicians and patients.

Estimating the value of surgical clips for target volume delineation in external beam partial breast radiotherapy.

AIMS: To investigate the role of surgical clips in defining the clinical target volume (CTV) for three-dimensional conformal external beam radiotherapy-partial breast irradiation (3D-CRT-PBI) using preoperative computed tomography scans. MATERIALS AND METHODS: A group of patients with early breast cancer underwent conservative surgery with placement of surgical titanium clips (at least three clips required). All patients had a treatment planning computed tomography simulation before (CT1) and after surgery (CT2). The two sets of images were co-registered with a match point registration. The relationship between the clips-based CTV for PBI delineated on CT2 and the initial tumour location on CT1 was studied, evaluating the percentage of intersection volume. RESULTS: Twenty-eight patients participated in this study. In total, 13 patients (46.4%) had an intersection volume ≥ 50% and 10 patients (35.7%) had complete intersection (intersection volume = 100%). An increased median intersection volume was observed in patients with more than six clips (P = 0.007) and in patients with a larger portion of breast volume covered by the PBI-CTV (CTV/BV; P = 0.010). Intersection volume increased with the number of clips, after adjustment for CTV/BV (linear coefficient = 5.1693; P = 0.043). Also, a maximum distance from the chest wall ≤0.7 cm and CTV/BV > 9.5% were found to be predictors of an intersection volume ≥50% (area under the curve 0.841; confidence interval 0.649-0.952; P < 0.0001; area under the curve 0.800; confidence interval 0.607-0.926; P = 0.0004) and of an intersection volume of 100% (area under the curve 0.776, confidence interval 0.573-0.916, P = 0.046; area under the curve 0.752, confidence interval 0.536-0.935; P = 0.032). CONCLUSIONS: Titanium clips are essential and six or more increase the accuracy of tumour bed delineation for PBI; also the primary tumour location as well as the percentage of volume of breast covered by PBI-CTV may influence the correct delineation of PBI-CTV.

MR imaging of rectal cancer before and after chemoradiation therapy.

PURPOSE: This study was done to determine the diagnostic accuracy of magnetic resonance (MR) imaging in patients with rectal carcinoma by comparing post-chemoradiation MR imaging with pathological specimens. MATERIALS AND METHODS: We enrolled 39 patients with locally advanced rectal cancer. All patients received chemoradiation therapy before surgery and neoadjuvant chemoradiation therapy followed by MR imaging. MR images were analysed by a team of two expert radiologists unaware of the clinical and histopathological findings. RESULTS: Following neoadjuvant chemoradiation therapy, the analysis of MR images showed 23 (59%) patients with a rectal disease staged ≤T2 and 16 (41%) with a disease staged >T2. Post-treatment histological staging (TNM) revealed 13 patients with a disease >T2 and 26 patients with a disease ≤T2. Cohen's kappa to measure concordance between post-chemoradiation MR staging and histological response showed 83.6% concordance for disease confined to the serosa (≤T3): concordance was 97.22% for disease ≤N1 and 33.33% for disease >N1. CONCLUSIONS: MR imaging is critical for discovering T3 disease; moreover, morphological MR imaging does not always provide the opportunity to discern small residual cancer cells hidden in fibrotic tissue that could cause involvement of circumferential resection margin (CRM) on histology.

[Occult mediastinal node involvement in non-small cell lung cancer after negative uptake on PET/CT: ripples through staging and therapy. Case report and critical review]. / Linfonodi mediastinici "occulti" nel NCCLC: ripercussioni della falsa negatività PET/TC sulla stadiazione e sulla terapia. Caso clinico e rassegna critica.

A 78-years old man, heavy smoker, with a persistent and hacking cough, was diagnosed with an adenocarcinoma of upper lobe of left lung. Clinical stage was defined as cT2N0M0 also on the basis of a negative (18)FDG-PET/TC. After lobectomy, pathological stage resulted, on the contrary, pT2N2M0. Because the considerable incidence of preoperative false negative uptakes of PET/TC for involvement of mediastinal lymph nodes, this case report is highlighted as emblematic, particularly in relation to post-operative treatment of early stage NSCLC.

Induction cisplatin-gemcitabine-paclitaxel plus concurrent radiotherapy and gemcitabine in the multimodality treatment of unresectable stage IIIB non-small cell lung cancer.

BACKGROUND: To evaluate feasibility and safety of induction three-drugs combination chemotherapy and concurrent radio-chemotherapy in stage IIIB NSCLC. PATIENTS AND METHODS: Patients with stage IIIB NSCLC were treated with three courses of induction chemotherapy, cisplatin 50 mg/m(2), paclitaxel 125 mg/m(2) and gemcitabine 1000 mg/m(2) on days 1,8 of every 21 day cycle. Patients without distant progressive disease were then treated with radiotherapy and concurrent weekly gemcitabine (250 mg/m(2)). Toxicity and response of radio-chemotherapy treatment have been assessed. RESULTS: Between Jan 01 and Nov 02, 46 patients were enrolled. Grade 3+ hematological and non-hematological toxicity during the induction phase were 41.3% and 13.1%, respectively. In 38 patients a Clinical Response or Stable Disease was recorded and these patients underwent to concurrent radio-chemotherapy. Grade 3+ hematological and non-hematological toxicities were 8.2% in this group. Further response was observed in 66% of patients. Overall median survival time was 17.8 months, with a 3-year survival rates of 23%. CONCLUSION: Three-drugs induction chemotherapy and concurrent radio-chemotherapy with weekly gemcitabine in locally advanced stage IIIB NSCLC is feasible and safe.

Chemo-radiotherapy in non-small cell lung cancer: the role of gemcitabine.

Gemcitabine (2'-2'-difluorodeoxycytidine) is a well-known cytotoxic drug and a potent radio-enhancer. We herein report the in vitro evidence of its activity, and the clinical experiences when this drug is administered concurrently with radiation. The phase I-II trials are analyzed, focusing on the recent ability to deliver irradiation with low incidence of side effects.

Complementary use of local excision and transanal endoscopic microsurgery for rectal cancer after neoadjuvant chemoradiation.

BACKGROUND: Neoadjuvant therapies have significantly improved local control and survival of patients with rectal cancer. Nevertheless, although a complete pathologic response can be achieved in 30% of cases, a transabdominal surgical resection is always required. This study aimed, for the first time, to test in the literature the feasibility of local excision combined with transanal endoscopic microsurgery (TEM) as a surgical option for patients treated with neoadjuvant chemoradiation. METHODS: Between July 1997 and December 2002, 30 patients with rectal cancer affected by an extraperitoneal tumor entered a protocol consisting of neoadjuvant chemoradiation followed by surgery. The surgical treatment, consisting of open surgery, local excision, or TEM, was planned according to the patient's clinical response after chemoradiation and distance from the anal verge. RESULTS: A significant clinical downstaging was observed in eight patients. Five of these patients underwent TEM, and three had local excision. Consequently, open surgery was performed for 22 patients. Histology showed six cases of complete pathologic response: three in the open surgery group and three in the transanal excision group. After a mean follow-up period of 47 months, the disease-free survival rate was 77% in the open surgery group and 100% in TEM or local excision group. CONCLUSIONS: The findings suggest the complementary feasibility of TEM and local excision after neoadjuvant chemoradiation. However, randomized trials are needed to confirm the oncologic safety of this approach.

Cetuximab and irinotecan as third-line therapy in advanced colorectal cancer patients: a single centre phase II trial.

The epidermal growth factor receptor (EGFR), which participates in signalling pathways that are deregulated in cancer cells, is frequently mutated in colorectal-cancer cells. Cetuximab is a monoclonal antibody that specifically blocks the EGFR. We evaluated the efficacy of cetuximab in weekly combination with irinotecan in metastatic colorectal cancer patients refractory to previous treatments based on oxaliplatin or irinotecan. We included 55 heavily pretreated patients (colon/rectum: 34/11, M/F: 16/29, median age 63 years, range: 27-79) whose disease had progressed during or within an oxaliplatin-based first-line chemotherapy and a irinotecan-based second-line regimen. Patients were followed for tumour response and were also evaluated for the time to tumour progression, and safety of treatment. Cetuximab was given at an initial dose of 400 mg m(-2), followed by weekly infusions of 250 mg m(-2). Irinotecan was administered weekly at the dose of 90 mg m(-2). All patients were assessable for treatment efficacy and safety response rate was 25.4% (95% CI: 21.7-39.6%); 38.2% (95 CI: 18.6-39.8%) of patients showed a disease stability as the best response. As a consequence, the overall tumour control rate was 63.6% (95% CI: 46.4-70.6%). The median time to progression was 4.7 months (95% CI: 2.5-7.1 months) and the median survival time was 9.8 months (95% CI: 3.9-10.1 months). The most common G3-4 noncutaneous side toxicities were: diarrhoea (16.4%), fatigue (12.7%) and stomatitis (7.3%). 89.1% of patients developed skin toxicity and 32.6% of cases was of grade 3-4. No allergic reactions were identified at any courses in any patients. Fever was documented in 27.3% of patients and was most commonly recorded after the first administration. Cetuximab has clinically significant activity even in heavily pretreated colorectal cancer patients progressed after both oxaliplatin and irinotecan-based chemotherapy regimens.

Autofluorescence bronchoscopy to identify pre-cancerous bronchial lesions.

BACKGROUND: This study aimed to assess the diagnostic yield of autofluorescence bronchoscopy (AFB) in the detection of pre-cancerous bronchial lesions in a non-selected sample of patients. METHODS: Both fiberoptic white-light bronchoscopy (WLB) and AFB using the Storz D-light system were performed on 166 consecutive patients. Biopsy specimens were taken in areas of the tracheobronchial tree judged as abnormal or suspicious at WLB and/or AFB. The bronchoscopic procedures were randomly performed by two operators. RESULTS: A total of 93 patients had a positive biopsy specimen: 80 for cancer and 13 for dysplasia. AFB was abnormal or suspicious in 85 of the 93 patients with a sensitivity of 91.4%. Specificity was 50.7%. In 16 patients with normal WLB examination, AFB identified abnormal or suspicious areas which had a positive biopsy. Thus AFB significantly improved sensitivity of WLB (100% vs 82.8%, respectively, p<0.001) in the entire sample of patients studied. Data was further analysed separately for patients with dysplasia and those with cancer. Indeed, 13 of 16 patients recognized only by AFB had a histological diagnosis of dysplasia. The remaining three patients had a diagnosis of cancer (small intraepithelial neoplastic lesions). Since no other patient with dysplasia was found, AFB had a sensitivity of 100% in diagnosing dysplasia. On the other hand, excluding the 13 patients with dysplasia, WLB had a high sensitivity in diagnosing cancer (93.7%). CONCLUSIONS: The AFB Storz system showed a high sensitivity. The increase in diagnostic yield of AFB in comparison with WLB was related to the power of AFB to identify pre-cancerous bronchial lesions so showing its usefulness in the early diagnosis of lung cancer.

Neoadjuvant concurrent radiochemotherapy in locally advanced (IIIA-IIIB) non-small-cell lung cancer: long-term results according to downstaging.

BACKGROUND: To report the efficacy of induction treatment (IT) protocol with concurrent radiochemotherapy in locally advanced non-small-cell lung cancer (NSCLC), and to analyze downstaging as a surrogate end point. PATIENTS AND METHODS: Patients with histo- or cytologically confirmed stage IIIA or IIIB NSCLC were treated according to an IT protocol followed by surgery. Downstaging was assessed for all resected patients. RESULTS: In the period between February 1992 and July 2000, 92 patients were enrolled in the study (57 IIIA, 35 IIIB). Response was observed in 63 patients; 56 patients underwent radical resection. Patients downstaged to stage 0-I (DS 0-I) showed a statistically significant improved disease-free survival (26.2 months pStage 0-I versus 11.2 months pStage II-III; P=0.0116) and overall survival (median 32.5 months pStage 0-I versus 18.3 months pStage II-III; P=0.025). Patients with DS 0-I had a significantly lower probability (P=0.0353) of developing distant metastases estimated in 0.2963 odds ratio. CONCLUSION: Neoadjuvant radiochemotherapy is feasible with good pathological DS results. Pathological downstaging was confirmed to have high predictive value. Its use is suggested in the short-term evaluation of induction protocols efficacy in locally advanced NSCLC.

Concomitant gemcitabine (Gemzar) and extended nodes irradiation in the treatment of pancreatic and biliary carcinoma: a phase I study.

BACKGROUND: The rationale for combining cytotoxic agents, such as gemcitabine, and radiotherapy is based on their ability to act as radiation sensitizers and to improve overall response rate. Several studies on pancreatic or biliary carcinoma evaluated the maximum tolerated dose (MTD) of gemcitabine when combined with irradiation of the macroscopic tumor. However, most of these neoplasms metastasize to the regional lymph nodes. Aim of this report is to determine the MTD of weekly gemcitabine when combined with extended field irradiation (tumor plus nodal irradiation). PATIENTS AND METHOD: 15 patients entered the study. Of these 5 patients were treated with chemoradiation after radical surgical resection. External beam radiation (ERT) was delivered to the tumor (or tumor bed) and regional lymph nodes by using a three-field technique. The initial dose of gemcitabine was 100 mg/m(2) administered as short intravenous infusion once a week. At each dose level 3 patients were treated, and if no grade 3-4 toxicity (considered as dose-limiting toxicity, DLT) was recorded, dose escalation was applied with 50 mg/m(2) increments until the MTD was established. RESULTS: All patients were evaluable for acute toxicity. There were no treatment-related deaths. No DLT occurred at the first 4 dose levels (100-250 mg/m(2)). At the 5th dose level (300 mg/m(2)), 3 patients experienced DLT: 1 had grade 3 gastrointestinal toxicity (painful erosion of gastric mucosa), 1 had uncomplicated grade 3 leukopenia and 1 grade 3 change in liver biochemistry tests. In addition, all 10 unresected patients were evaluated for response, 4 of whom had progressive disease (1 local; 2 distant; 1 local and distant) and 6 had no change. The median follow-up was 21 months. CONCLUSION: Based on this study, the recommended dose for weekly short infusional gemcitabine combined with radiation therapy to the tumor and lymph nodes is 250 mg/m(2). This value is suggestive of a correlation between acute toxicity and inclusion of lymph nodes in the irradiated volume. Moreover, different infusion modalities, as continuous infusion gemcitabine, should be tested more accurately.