Radiotherapy activities and technological equipment in Veneto, Italy: a report from the Rete Radioterapica Veneta.

BACKGROUND: Despite the pivotal role of radiotherapy in oncology, the provision of radiation treatments remains inadequate in many areas of the world. The present report is an assessment conducted among Radiation Oncology centers of Veneto region with the aim to collect information concerning radiotherapy assets and technological equipment availability. METHODS: Data concerning Veneto Radiation Oncology departments about radiotherapy activities, number of treatments, techniques used and radiotherapy machines available were collected. The reference time period was 2018. Reimbursement system databases and business intelligence systems were used. Extra-regional attraction and migration were evaluated. When available, data were compared to previous years. RESULTS: Veneto in 2018 was endowed with 1 megavolt unit for about 153,000 inhabitants. The number of megavolt machines per million inhabitants resulted to be 6.72. In 51% of radiotherapy treatments, intensity-modulated techniques were performed. Six percent of treatments were administered to extra-regional patients. CONCLUSION: Radiotherapy assets and equipment in Veneto seem to be appropriate to standard requests in terms of availability and technology.

The activity and safety of electrochemotherapy in persistent chest wall recurrence from breast cancer after mastectomy: a phase-II study.

Electrochemotherapy (ECT) represents an attractive locoregional therapy for unresectable chest wall recurrence (CWR) from breast cancer. Thirty-five patients with cutaneous CWR after mastectomy who experienced progression despite re-irradiation and extensive systemic treatments were administered bleomycin-based ECT. Local response, toxicity, and superficial control were evaluated. Out of 516 metastases (median 15/patient, range 1-50), response was assessed on 196 target lesions (median size 20 mm, range 10-220). Patients received a median of 2 ECT courses (range 1-3). Two-month objective response was as follows: 54.3 % complete (19/35 patients), 37.1 % partial (13/35), and 8.6 % no change (3/35). Twenty-three patients (65.7 %) developed new lesions (NL) after a median time of 6.6 months (range 2.3-29.5), therefore 1, 2, or 3 ECT cycles were required in 14, 15, and 6 patients, respectively. Median follow-up was 32 months (range 6-53) and the 3-year local control rate was 81 %. Related morbidity was mild, increased after retreatments and consisted primarily of pain (reported as "moderate"/"severe" by 6, 13, and 17 % of patients 1 month after the first, second, and third application, respectively) and dermatological toxicity (acute G3 skin ulceration in 14, 20, and 33 % of patients, respectively). Less than 10 metastases (P < 0.001), the narrower area of tumor spread on the chest wall (P = 0.022), complete response achievement (P = 0.019), and post-ECT endocrine instead of chemotherapy (P = 0.025) were associated to NL-free survival. Only fewer skin metastases, hazard ratio (HR) 0.122, 95 % confidence interval (CI) 0.037-0.397, P < 0.001, and contained superficial spread, HR 0.234, 95 % CI 0.067-0.818, P = 0.023, were predictors for longer NL-free survival. ECT showed a satisfactory activity in refractory breast cancer CWR, providing sustained local control. Patients with fewer and less scattered skin metastases are less likely to develop NL. Partial responders and NL can be handled with additional ECT albeit increasing local pain and skin toxicity.

The role of stereotactic body radiation therapy and its integration with systemic therapies in metastatic kidney cancer: a multicenter study on behalf of the AIRO (Italian Association of Radiotherapy and Clinical Oncology) genitourinary study group.

Although systemic therapy represents the standard of care for polymetastatic kidney cancer, stereotactic body radiation therapy (SBRT) may play a relevant role in the oligometastatic setting. We conducted a multicenter study including oligometastatic kidney cancer treated with SBRT. We retrospectively analyzed 207 patients who underwent 245 SBRT treatments on 385 lesions, including 165 (42.9%) oligorecurrent (OR) and 220 (57.1%) oligoprogressive (OP) lesions. Most common sites were lung (30.9%) for OR group, and bone (32.7%) for OP group. Among 78 (31.8%) patients receiving concomitant systemic therapy, sunitinib (61.5%) and pazopanib (15.4%) were the most common for OR patients, while sunitinib (49.2%) and nivolumab (20.0%) for OP patients. End points were local control (LC), progression free survival (PFS), overall survival (OS), time to next systemic therapy (TTNS) and toxicity. Median follow-up was 18.6 months. 1, 2 and 3-year LC rates were 89.4%, 80.1% and 76.6% in OR patients, and 82.7%, 76.9% and 64.3% in those with OP, respectively. LC for OP group was influenced by clear cell histology (p = 0.000), total number of lesions (p = 0.004), systemic therapy during SBRT (p = 0.012), and SBRT dose (p = 0.012). Median PFS was 37.9 months. 1, 2- and 3-year OS was 92.7%, 86.4% and 81.8%, respectively. Median TTNS was 15.8 months for OR patients, and 13.9 months for OP patients. No grade 3 or higher toxicities were reported for both groups. SBRT may be considered an effective safe option in the multidisciplinary management of both OR and OP metastases from kidney cancer.

Interval between neoadjuvant chemoradiotherapy and surgery for squamous cell carcinoma of the thoracic esophagus: does delayed surgery have an impact on outcome?

OBJECTIVE: Aim of this study was to evaluate whether delayed surgery after neoadjuvant chemoradiotherapy (CRT) affects postoperative outcomes in patients with locally advanced squamous cell carcinoma (SCC) of the thoracic esophagus. BACKGROUND: Esophagectomy is usually recommended within 4 to 6 weeks after completion of neoadjuvant CRT. However, the optimal timing of surgery is not clearly defined. METHODS: A total of 129 consecutive patients with locally advanced esophageal cancer, treated between 1998 and 2007, were retrospectively analyzed using prospectively collected data. Patients were divided into 3 groups on the basis of timing to surgery: group 1, ≤30 days (n = 17); group 2, 31 to 60 days (n = 83); and group 3, 61 to 90 days (n = 29). Subsequently, only 2-numerically more consistent-groups were studied, using the median value of timing intervals as a cutoff level: group A, ≤46 days (n = 66); and group B, >46 days (n = 63). RESULTS: Groups were comparable in terms of patient and tumor characteristics, type of neoadjuvant regimen, toxicity, postoperative morbidity and mortality rates, tumor downstaging, and pathologic complete responses. The overall 5-year actuarial survival rate was 0% in group 1, 43.1% in group 2, and 35.9% in group 3 (P = 0.13). After R0 resection (n = 106), the 5-year actuarial survival rate was 0%, 51%, and 47.3%, respectively (P = 0.18). Tumor recurrence after R0 resection seemed to be inversely related, even if not significantly (P = 0.17), to the time interval between chemoradiation and surgery: 50% in group 1, 40.6% in group 2, and 21.7% in group 3. When considering only 2 groups, the overall 5-year survival was 33.1% in group A and 42.7% in group B (P = 0.64); after R0 resection, the 5-year survival was 37.8% and 56.3%, respectively (P = 0.18). The rate of tumor recurrence was significantly lower in group B (25%) than in group A (48.3%) (P = 0.02). CONCLUSION: Delayed surgery after neoadjuvant chemoradiation does not compromise the outcomes of patients with locally advanced SCC of the esophagus. Delaying surgery up to 90 days offers relevant advantages in the clinical management of the patients, can reduce tumor recurrences, and may improve prognosis after complete R0 resection surgery.

Bleomycin-based electrochemotherapy: clinical outcome from a single institution's experience with 52 patients.

Electrochemotherapy (ECT) has emerged as a complementary treatment for superficial metastases. Fifty-two consecutive patients with different cancer histotypes, mainly melanoma and breast cancer, with disease unsuitable for conventional treatments underwent bleomycin-based ECT for cutaneous and subcutaneous metastases. Toxicity, local response, response duration, and the impact on quality of life were evaluated. A total of 608 tumor nodules were treated (mean, 12 per patient), with 27% of patients affected by nodules >3 cm in size. Treatment was tolerated well, especially under general sedation. An objective response was obtained in 50 (96%) of 52 patients 1 month after the first application. Twenty-two patients underwent a second treatment (because of partial response or the appearance of new lesions). Partial response at first ECT achieved a response consolidation at second application: 80% complete response, 20% partial response. Some patients underwent up to five treatments because of new lesions, but maintained superficial tumor control. After a mean follow-up of 9 (range, 2-21) months, only two patients experienced relapse in the treatment field. Through a nonvalidated eight-item questionnaire (assessing wound healing and bleeding, aesthetic impairment, daily activities, social relations, pain, treatment satisfaction, acceptance of retreatment), most patients reported a benefit in local disease-related complaints and in activity of daily living. In a palliative setting, ECT proved to be safe, effective in all tumors treated, and useful in preserving patients' quality of life. This benefit, although preliminary, deserves further assessment after a formal validation of the dedicated questionnaire.

Individual Radiosensitivity in Oncological Patients: Linking Adverse Normal Tissue Reactions and Genetic Features.

Introduction: Adverse effects of radiotherapy (RT) significantly affect patient's quality of life (QOL). The possibility to identify patient-related factors that are associated with individual radiosensitivity would optimize adjuvant RT treatment, limiting the severity of normal tissue reactions, and improving patient's QOL. In this study, we analyzed the relationships between genetic features and toxicity grading manifested by RT patients looking for possible biomarkers of individual radiosensitivity. Methods: Early radiation toxicity was evaluated on 143 oncological patients according to the Common Terminology Criteria for Adverse Events (CTCAE). An individual radiosensitivity (IRS) index defining four classes of radiosensitivity (highly radiosensitive, radiosensitive, normal, and radioresistant) was determined by a G2-chromosomal assay on ex vivo irradiated, patient-derived blood samples. The expression level of 15 radioresponsive genes has been measured by quantitative real-time PCR at 24 h after the first RT fraction, in blood samples of a subset of 57 patients, representing the four IRS classes. Results: By applying univariate and multivariate statistical analyses, we found that fatigue was significantly associated with IRS index. Interestingly, associations were detected between clinical radiation toxicity and gene expression (ATM, CDKN1A, FDXR, SESN1, XPC, ZMAT3, and BCL2/BAX ratio) and between IRS index and gene expression (BBC3, FDXR, GADD45A, and BCL2/BAX). Conclusions: In this prospective cohort study we found that associations exist between normal tissue reactions and genetic features in RT-treated patients. Overall, our findings can contribute to the identification of biological markers to predict RT toxicity in normal tissues.

Neoplastic Pericardial Effusion: A Monocentric Retrospective Study.

Background: Neoplastic pericardial effusion (NPE) is a life-threatening condition that can worsen clinical outcome in cancer patients. The optimal management of NPE has yet to be defined because randomized studies are lacking. Objective: We report a retrospective monoinstitutional experience describing characteristics, management and prognostic factors in NPE patients. Design: We reviewed clinical, pathological, and echocardiographic features, therapeutic strategies, and outcome in NPE patients referred to our institute from August 2011 to December 2017. Measurements: Twenty-nine patients with NPE from solid tumors have been identified: 21 lung, 5 breast, and 3 other cancer patients. Results: Median age was 62 years. Most of the patients had Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥2 (69%) and a symptomatic NPE (69%). In 52% of patients NPE was detected at first diagnosis of metastatic disease, and in 20% of patients pericardium was the only site of metastases. Most of the patients (62%) received systemic therapy, 28% received combined locoregional and systemic therapy, and 10% received locoregional therapy alone. Median overall survival (OS) from NPE diagnosis was 3.9 months. Patients with PS ≥2 had worse OS than patients with better PS <2 (hazard ratio [HR] 3.56, IC 95% 1.19-10.65, p 0.02). Older age, extrapericardial disease, and NPE at progression showed a trend of association with worse OS. Patients treated with locoregional therapy alone showed the shortest median OS (p 0.05). Conclusions: NPE is related to dismal prognosis. Poor PS significantly worsens survival and influences therapeutic approaches. Randomized studies are required to investigate prognostic factors and appropriate clinical management for patients with NPE.

Effects of neoadjuvant therapy on perioperative morbidity in elderly patients undergoing esophagectomy for esophageal cancer.

BACKGROUND: The use of cytoreductive therapy followed by surgery is preferred by many centers dealing with locally advanced esophageal cancer. However, the potential for increase in mortality and morbidity rates has raised concerns on the use of chemoradiation therapy, especially in elderly patients. The aim of this study was to assess the effects of induction therapy on postoperative mortality and morbidity in elderly patients undergoing esophagectomy for locally advanced esophageal cancer at a single institution. METHODS: Postoperative mortality and morbidity of patients > or = 70 years old undergoing esophagectomy after neoadjuvant therapy, between January 1992 and October 2005 for cancer of the esophagus or esophagogastric junction, were compared with findings in younger patients also receiving preoperative cytoreductive treatments. RESULTS: 818 patients underwent esophagectomy during the study period. The study population included 238 patients < 70 years and 31 > or = 70 years old undergoing esophageal resection after neoadjuvant treatment. Despite a significant difference in comorbidities (pulmonary, cardiological and vascular), postoperative mortality and morbidity were similar irrespective of age. CONCLUSIONS: Elderly patients receiving neoadjuvant therapies for cancer of the esophagus or esophagogastric junction do not have a significantly increased prevalence of mortality and major postoperative complications, although cardiovascular complications are more likely to occur. Advanced age should no longer be considered a contraindication to preoperative chemoradiation therapy preceding esophageal resection in carefully selected fit patients.

Treatment of chemotherapy-induced oral mucositis with light-emitting diode.

OBJECTIVE: The aim of this study was to assess the clinical effectiveness of phototherapy with noncoherent light in the alleviation of chemotherapy-induced mucositis in patients with metastatic cancer. BACKGROUND DATA: Mucositis occurs in more than 40% of chemotherapy-treated patients, significantly reducing the quality of their lives. Many different interventions have been evaluated to reduce oral mucositis. Recently, good results have been achieved by phototherapy with photoradiation, a technique which has virtually no side effects. Some clinical results seem to indicate that also phototherapy through noncoherent light emissions which can be produced by less expensive light sources such as light-emitting diodes (LEDs) may be effective. However, until now, no studies have been available on this subject. METHODS: Twelve patients, aged from 34 to 82, selected on the basis of a diagnosis of chemotherapy-induced oral mucositis, were treated intra-orally through a noncoherent LED emission, wavelength 645 +/- 15 nm, 7.8 mW, fluence 0.99 J/cm(2), three times a day for 1 week. Mucositis was scored daily using the Daily Mucositis Index (DMI), a scale that evaluates the disease evolution through 16 different items. The primary end-point assessed was the time to recovery, from the start of LED treatment, compared to a nonrandomized control group of 12 patients with comparable stomatitis. RESULTS: The median healing time, expressed as the DMI decrease, was 1.7 (range 1-2.8) and, in seven LED-treated patients, was shorter than in the control group. The healing rate (measured as the ratio of the DMIs) increased from 117% to 164%. CONCLUSION: This pilot study shows that LED treatment is safe and capable of reducing the duration of chemotherapy-induced mucositis. This result needs to be confirmed in an adequate phase III study.

[Multimodal treatment in locally advanced esophageal cancer: a multicenter phase II study with neoadjuvant oxaliplatin, 5-fluorouracil, leucovorin and neoadjuvant radiotherapy: preliminary results]. / Il trattamento multimodale del carcinoma esofageo localmente avanzato. Trial multicentrico di fase II con oxaliplatino, 5-fuoroziacile, folati ridotti e radioterapia neoadiuvanti: risultati prelirninari.

The aim of the study was to evaluate the feasibility and efficacy of treatment with oxaliplatin, 5-fluorouracil and leucovorin concomitant with radiation therapy in locally advanced oesophageal cancer. Fifty-eight patients with previously untreated, histologically proven oesophageal cancer were enrolled. Downstaged patients underwent either surgery or received brachytherapy. We report the results obtained in the first 54 patients. The median age was 58 years. The diagnosis was squamous cell carcinoma/adenocarcinoma/poorly differentiated: 45/8/1; clinical stage: T3N1M0 38 (70%), T4 10 (19%), M1a 6 (11%). Thirty-nine patients (72%) received the planned 8 weeks of chemotherapy and 45 completed the entire course of scheduled radiotherapy. Four (7%) toxic deaths were recorded, 2 more patients died prematurely from massive oesophageal bleeding and 1 from progression of disease. We recorded 8 (15%) complete responses and 24 (44%) partial responses. Resection was complete (R0) in 24 (80% of resected patients, 44% of treated patients). A complete pathological response was documented in 6 patients (11% of those treated). Postoperative complications were recorded in 8 (25%) patients, with 2 (6.2%) deaths. RO resection was accomplished in 44% of patients. Toxicity was moderate, but postoperative mortality was not negligible. Survival data are awaited before a phase III comparison with cisplatin-containing chemo-radiotherapy may be considered.

[Electrochemotherapy: mechanism of action and clinical results in the locoregional treatment of patients with skin cancers and superficial metastases]. / Elettrochemioterapia: meccanismo d'azione e risultati del trattamento locoregionale nei pazienti con tumori cutanei e metastasi superficiali.

Electrochemotherapy (ECT) has emerged among European centers as an innovative locoregional treatment for patients with unresectable skin cancers or superficial metastases from any histotype. The combined administration of a cytotoxic agent (bleomycin or cisplatin) with properly tuned electric pulses results in locally-enhanced drug delivery (reversible electroporation) into malignant cells and sustained tumor response. Reversible electroporation represents the basis of ECT and allows the potentiation of two low permeant cytotoxic agents such as bleomycin (~8000 fold) and cisplatin (~80 fold). The procedure was standardized in 2006 - thanks to a European project - and shortly after introduced in the clinical practice. In recent years, experience with ECT has accumulated mainly in melanoma and breast cancer patients with cutaneous metastases, in whom complete response rates of 20-50% and 40-75% have been reported, respectively, depending on tumor size. Currently, this therapy is being investigated in deep-seated (i.e. bone, soft tissue) metastases and visceral malignancies (i.e. locally advanced pancreatic cancer), with encouraging results.

Successful use of a topical mixture with ozolipoile in the treatment of actinic ulcers.

PURPOSE: Post-radiation skin damage is the result of alterations produced in the irradiated zone. There are different studies aimed at verifying the effectiveness of several kinds of molecules in the treatment of radiation-induced skin damage. The purpose of this study is to test a mixture with a formulation containing several natural active ingredients on actinic ulcers in patients receiving radiation therapies. PATIENTS AND METHODS: The authors recruited 13 patients, and randomly divided them into a test group (T1) and a control group (T2). The patients in both groups were undergoing radiotherapy. The T1 group was treated with a mixture called ozolipoile, whereas the T2 group was administered hyaluronic acid gel followed by non-ablative laser therapy. We evaluated the obtained results, the time of clinical healing, the reduction of pain, and each side effect, comparing all data between the T1 and T2 groups. RESULTS: The average Visual Analog Scale results showed decrease in pain in both groups; however, while the T1 group showed a significant decrease in the values, the T2 group reported a more gradual reduction in the values, without ever reaching the minimum values obtained with the treatment with ozolipoile. CONCLUSION: Treatment of actinic ulcers with ozolipoile mixture leads to faster control of pain and to better healing of small-size ulcers.

Radiation therapy combined with photofrin or 5-ALA: effect on Lewis sarcoma tumor lines implanted in mice. Preliminary results.

AIMS AND BACKGROUND: Ionizing irradiation is a well-established therapeutic modality for cancer. Photodynamic therapy (PDT), especially with 5-ALA and Photofrin, is highly effective in some tumor types. Chemical modifiers, so-called radiosensitizers, are used in order to increase the efficacy of radiotherapy. Most of the known and routinely used radiosensitizers are not tumor selective, so that the normal tissue reaction toxicity is also increased. In the present study we investigated whether a porphyrin derivative that is currently used as a tumor-photosensitizing agent in photodynamic therapy (PDT) may also act as a tumor-specific radiosensitizer. MATERIALS AND METHODS: For our investigation we used Balb/c mice implanted with Lewis sarcoma and irradiated with 3 Gy combined with injection of 5-ALA or Photofrin at various concentrations before irradiation. RESULTS: 5-ALA had no effect as a radiosensitizer at any of the concentrations examined. Photofrin at a concentration of 5 mg/kg proved to be a chemical modifier of ionizing radiation, delaying tumor growth and reducing the overall tumor volume by about 50% after six days. CONCLUSION: Photofrin has marked efficacy as a radiosensitizer and can be used in the future as a selective tumor radiosensitizer.

Cell growth modulation of human cells irradiated in vitro with low-level laser therapy.

OBJECTIVE: The aim of this study was to investigate the effects of different wavelengths and doses of laser radiation on in vitro cell proliferation. We evaluated the biological effects of low-level laser therapy (LLLT) on two human cancer cell lines: HeLa (epithelial adenocarcinoma) and TK6 (lymphoblast). Our attention was focused on the combination of the two laser emissions as it could have a synergic effect greater than the single emission applied separately. BACKGROUND DATA: The effects of LLLT on human cells are still poorly understood and unexplained. Several cell types were found non responsive to laser bio stimulation; in other cases, only a partial activation was observed. METHODS: A laser device was used for cell irradiation with a continuous wave diode (lambda = 808 nm), a pulsed wave diode (lambda = 905 nm), and a combined wave diodes (lambda = 808 nm + 905 nm), in the dose range of 1-60 J/cm(2). RESULTS: The effect of the combined low-level 808-905-nm diode laser irradiation were slightly superior to those achieved with either laser alone in HeLa cells. TK6 cellular proliferation was not found to be significantly affected by any of the energy levels and varying exposure doses investigated. CONCLUSIONS: Our results are a confirmation of previous observations carried out on human cells, where only the proliferation of slowly growing cell populations appeared to be stimulated by laser light.

Complete clinical response after neoadjuvant chemoradiotherapy for squamous cell cancer of the thoracic oesophagus: is surgery always necessary?

BACKGROUND: Neoadjuvant chemoradiotherapy (CT-RT) before oesophagectomy is standard management for squamous cell carcinoma(SCC) of the thoracic oesophagus. The aim of this study was to compare the outcome of patients who had clinical complete response(CR) with neoadjuvant CT-RT + oesophagectomy with the survival of patients who had clinical CR and were not operated on. PATIENTS AND METHODS: Seventy-seven consecutive patients with SCC of the thoracic oesophagus with CR with neoadjuvant CT-RT presenting at the Regional Center of Esophageal Diseases from 1992 to 2008 were included in this retrospective study on a prospectively collected database. Thirty-nine patients underwent oesophagectomy (CT-RT + oesophagectomy), while 38(CT-RT) were not operated on because they were considered unfit for surgery or refused the operation. Patients' outcome and survival were compared. RESULTS: In the CT-RT + oesophagectomy group, clinical CR was confirmed after histological examination of the surgical specimen in 27/39 (69.2 %) patients. Five-year overall survival rates were 50.0 % in the CT-RT + oesophagectomy group and 57.0 % in the CT-RT group (p=0.99); 5-year disease-free survival rates were 55.5%in the CT-RT + oesophagectomy group and 34.6%in the CTRT group (p=0.15). Even after adjusting for propensity score, age, ASA and clinical stage, the treatment regimen did not show a statistically significant effect on overall survival (adjusted p=0.65) nor on disease-free survival (adjusted p=0.15). CONCLUSION: In our group of patients with clinical CR after neoadjuvant CT-RT for SCC of the thoracic oesophagus, waiting for recurrence and then using salvage surgery did not negatively impact their survival compared to patients treated with surgery. More accurate restaging protocols are warranted to improve decision making after CR with neoadjuvant CT-RT.

Positron emission tomography/computed tomography and esophageal cancer in the clinical practice: How does it affect the prognosis?

AIMS: The aim of this study was to assess the diagnostic value of positron emission tomography/computed tomography (PET/CT) in staging of esophageal cancer and to evaluate the prognostic role of metabolic parameters before and after neo-adjuvant treatment. SETTINGS AND DESIGN: Mono-institutional retrospective study. MATERIALS AND METHODS: We retrospectively evaluated 29 patients who underwent PET/CT at initial staging and after neo-adjuvant therapy. Metabolic parameters were calculated: mean, average, maximum standardized uptake value (SUVmax), and total lesion glycolysis (TLG). Diagnostic advantages of PET/CT over conventional imaging (CI) were determined. The relationships between baseline and after-therapy SUVmax and TLG, change in SUV and TLG (reported as ∆) for the primary tumor and prognosis were assessed. STATISTICAL ANALYSIS USED: Non-parametric statistic (e.g. Wilcoxon test and chi-square test). RESULTS: Twenty-nine patients were eligible for the initial staging. Thirteen patients were incorrectly staged based on CI; PET/CT was able to identify distant lymph nodes in seven patients (59%) and distant metastases in four (31%). The median SUVmax before and after neoadjuvant therapy was 10.38 and 3.53 (P = 0.0005), respectively. Only few semi-quantitative parameters obtained by PET/CT after neoadjuvant therapy seemed to have a prognostic value. TLG and ∆TLG were significantly different between disease-free and died patients (0.49 versus 15.51 and 100% versus 94%, respectively; all P = <0.05). CONCLUSIONS: PET/CT is confirmed as being able to detect distant metastases and to avoid unnecessary surgery. Although not routinely reported, post-neoadjuvant TLG and ∆TLG might be considered as useful prognostic parameters and should be further evaluated prospectively.

Vulvar cancer: prognostic factors.

BACKGROUND: Prognostic factors such as surgery and pathology in vulvar squamous cell carcinoma are studied. PATIENTS AND METHODS: 47 patients with vulva squamous cell carcinoma treated at the Gynecology Department of the University of Padua, have been retrospectively studied. RESULTS: At the univariate relapse-free survival analysis, a significant association was found for histological grade, stage of disease and type of surgery. All patients presented vulvar squamous cell carcinoma: G(1) in 25 (53%), G(2) in 14 (30%), and G(3) in 8 (17%) patients. The distribution of stages was as following: stage 1 in 6 (13%), stage 2 in 20 (43%), stage 3 in 11 (23%), and stage 4 in 10 patients (21%). Radiotherapy was performed in 13 patients. Among the 47 patients evaluable: 26 (55.3%) developed local recurrence, 12 of these patients developed a second local relapse, 3 of these also had distant metastases (lung in 1 patient, lomboaortic and mediastinic lymph nodes in the other 2 patients). Stromal invasions were 9 mm in 30 patients with 27 relapses (univariated analysis p=0 0066). Five episodes (10,6%) of thrombosis were observed. CONCLUSION: After multivariate analysis, surgery, stage and stromal invasion over 9 mm (hazard ratio=3.1; 95% confidence interval: 1.3-7.7) proved to be the most dominant predictor for relapse-free survival. Histological grades 1 and 2 were predictive of better disease-free survival (p=0.0012).

A case of anaplastic thyroid cancer with long-term survival.

Anaplastic thyroid carcinoma (ATC) (less than 10% of all thyroid cancer) is a high-grade neoplasm, characterized by an aggressive clinical course and refractoriness to currently available local and systemic modalities of treatment. It is considered the most aggressive solid tumour, there is no adequate therapy for this disease and few patients with ATC live more than 1 year following diagnosis. We report herein an unusual case of ATC in a 59-year-old woman. She presented to our Institute in December 2004. She received many kinds of chemotherapeutical and multimodal treatment; we obtained a long period of localized disease (about two years) and an excellent response to therapy. She is still alive 58 months from diagnosis.

Multi-center phase II trial of chemo-radiotherapy with 5-fluorouracil, leucovorin and oxaliplatin in locally advanced esophageal cancer.

PURPOSE: The aim of this study was to evaluate the activity and safety of oxaliplatin/5-fluorouracil-based chemo-radiotherapy in patients with not radically resectable locally advanced esophageal cancer. METHODS: Fifty-nine patients with adeno or squamous-cell carcinoma received oxaliplatin (60 mg/m(2)), and leucovorin (20 mg/m(2) on days 1,8,15,29,36,43,50,57) followed by continuous infusion fluorouracil (200 mg/m(2) per day on days 1-22 and 29-64) with radiotherapy (1.8 Gy daily fractions to a total dose of 45 Gy, from days 29 to 64). When feasible, surgery was scheduled 6-8 weeks after chemo-radiotherapy completion. The primary endpoint was 1-year progression-free survival. RESULTS: Forty (68%) patients completed treatment without modifications. An objective clinical response was seen in 35 patients (59%). Esophagectomy was possible in 33 patients and a complete resection (R0) was achieved in 26 (79%) with 6 pathologic complete responses (pCR) and 3 near pCR. At a median follow-up of 39.7 months for the surviving patients, the median progression-free and overall survivals were 11 months (95% CI 6.5-14) and 18.5 months (95% CI 13-29). The 1-year progression-free and overall survivals were 47.5% (95% CI 34-59.5%) and 63% (95% CI 49-74%). Major toxicities were esophagitis (20% G3 and 5% G4) and diarrhea (8.5% G3 and 8.5% G4). Hematological toxicity (7% G3 and 3% G4) was less common; severe neurotoxicity (3% G3) was infrequent. CONCLUSIONS: Concurrent oxaliplatin, leucovorin, fluorouracil and radiotherapy followed or not by esophagectomy has a tolerable toxicity and promising activity in locally advanced esophageal cancer.

Trends in management and prognosis for esophageal cancer surgery: twenty-five years of experience at a single institution.

OBJECTIVE: To investigate trends in results of esophagectomies to treat esophageal cancer at a single high-volume institution during the past 25 years. DESIGN AND SETTING: Retrospective cohort study in a university tertiary referral center. PATIENTS AND METHODS: Patients with cancer of the thoracic esophagus or esophagogastric junction seen from 1980 through 2004 were included (N = 3493). Three time periods were defined: 1980-1987, 1988-1995, and 1996-2004. MAIN OUTCOME MEASURES: Clinical presentation, tumor characteristics, and morbidity, mortality, and survival rates among patients with esophageal cancer undergoing esophagectomy. RESULTS: The ratio of squamous cell carcinoma to adenocarcinoma decreased from 3.3 to 1.7 (P <.001) during the study period, in parallel with an increase in the number of patients with tumors in the lower esophagus/esophagogastric junction. An increasing proportion of patients who underwent resection received neoadjuvant treatment (chemotherapy/chemoradiotherapy), and 1978 patients underwent esophagectomy. The R0 resection rate increased from 74.5% to 90.1% (P <.001). In addition, an increasing proportion of patients had early-stage tumor in the resected specimen. In-hospital postoperative mortality decreased from 8.2% to 2.6% (P <.001), and the 5-year survival rate significantly improved from 18.8% to 42.3% (P <.001) for all patients who underwent resection. Pathological tumor stage, completeness of the resection, time period, sex, tumor histological type, and tumor location influenced the prognosis of patients with esophageal cancer undergoing esophagectomy. CONCLUSIONS: A change in location and histological type of esophageal cancer has occurred during the past 25 years. Earlier diagnosis, a multidisciplinary approach, and refinements in surgical technique and perioperative care have led to a significant reduction in postoperative mortality rate and improved long-term survival among patients with cancer of the thoracic esophagus or esophagogastric junction.