MRI-derived radiomics to guide post-operative management of glioblastoma: Implication for personalized radiation treatment volume delineation.

Background: The glioblastoma's bad prognosis is primarily due to intra-tumor heterogeneity, demonstrated from several studies that collected molecular biology, cytogenetic data and more recently radiomic features for a better prognostic stratification. The GLIFA project (GLIoblastoma Feature Analysis) is a multicentric project planned to investigate the role of radiomic analysis in GB management, to verify if radiomic features in the tissue around the resection cavity may guide the radiation target volume delineation. Materials and methods: We retrospectively analyze from three centers radiomic features extracted from 90 patients with total or near total resection, who completed the standard adjuvant treatment and for whom we had post-operative images available for features extraction. The Manual segmentation was performed on post gadolinium T1w MRI sequence by 2 radiation oncologists and reviewed by a neuroradiologist, both with at least 10 years of experience. The Regions of interest (ROI) considered for the analysis were: the surgical cavity ± post-surgical residual mass (CTV_cavity); the CTV a margin of 1.5 cm added to CTV_cavity and the volume resulting from subtracting the CTV_cavity from the CTV was defined as CTV_Ring. Radiomic analysis and modeling were conducted in RStudio. Z-score normalization was applied to each radiomic feature. A radiomic model was generated using features extracted from the Ring to perform a binary classification and predict the PFS at 6 months. A 3-fold cross-validation repeated five times was implemented for internal validation of the model. Results: Two-hundred and seventy ROIs were contoured. The proposed radiomic model was given by the best fitting logistic regression model, and included the following 3 features: F_cm_merged.contrast, F_cm_merged.info.corr.2, F_rlm_merged.rlnu. A good agreement between model predicted probabilities and observed outcome probabilities was obtained (p-value of 0.49 by Hosmer and Lemeshow statistical test). The ROC curve of the model reported an AUC of 0.78 (95% CI: 0.68-0.88). Conclusion: This is the first hypothesis-generating study which applies a radiomic analysis focusing on healthy tissue ring around the surgical cavity on post-operative MRI. This study provides a preliminary model for a decision support tool for a customization of the radiation target volume in GB patients in order to achieve a margin reduction strategy.

Silent thyroiditis following vaccination against COVID-19: report of two cases.

PURPOSE: It is well established that thyroiditis and other thyroid disorders can be induced by COVID-19 infection, but there is limited information about the autoimmune/inflammatory syndrome induced by adjuvants (ASIA) after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination. We report two cases of thyrotoxicosis following SARS-CoV-2 vaccine. METHODS AND RESULTS: Two young health care peoples (wife and husband) received a first dose of SARS-CoV-2 vaccine, and few weeks later developed clinical manifestations of thyroid hyperactivity, with increased thyroid hormone levels on thyroid function tests, suppressed thyroid-stimulating hormone and negative antithyroid antibodies, despite being healthy before vaccination. They were diagnosed at the 4th week after first dose of SARS-Cov-2 vaccine as silent thyroiditis and followed without treatment, since their symptoms were not severe. At the 6th week, the patients became wholly asymptomatic and their thyroid function returned to normal. CONCLUSIONS: Thyrotoxicosis can occur after SARS-CoV-2 vaccination probably related to silent thyroiditis.

Radiation therapy technologists' involvement and opinion in research: A national survey in Italy.

INTRODUCTION: This survey describes Italian RTTs' involvement and opinions in research activities related to radiation oncology. Primary aim was to assess the degree of involvement of the national RTTs community in research and to describe how RTTs can integrate their skills collaborating with other professionals. MATERIALS AND METHODS: A ten-items multiple-choice questionnaire, with 2-8 possible responses, was developed by a steering committee and generated on a survey platform. Links were sent via email to Italian RTTs.The questions were divided in 3 domains: demographic data; scientific research and activity; opinions about RTTs role in scientific research. The survey started on October 1, 2018 and ended on January 31, 2019. RESULTS: One hundred thirty-five out of 509 (26.5%) RTTs responded to the questionnaire at its expiring date; 97.73% think to be valid contributors in radiation oncology research, expressing clear interest in "data collection" tasks (52.71%); 38.64% feel unsupported by other professionals in the research team and 59.85% of the respondents are not members in any scientific society. CONCLUSIONS: The role of Italian RTTs in research is heterogeneous. Mainly RTTs in the age range from 30 to 40 years responded to the survey showing their interest in scientific research. This might be related to different informatics and educational skills as well as to personal attitudes. RTTs particular skills, like data management and technical hypothesis generation abilities, are of benefit to realize research projects. Therefore, engaging RTTs in research activities is strongly suggested.

IMproved MAnagement (IM-MA study) in cancer-related pain: the value of a joint approach by an integrated team of radiotherapist and anesthetist.

PURPOSE: Purpose of this study was to retrospectively review our experience of multidisciplinary clinic providing a joint approach by radiation oncologist and anesthetist for patients with cancer pain to evaluate the adequacy and the IMprovement in MAnagement (IM-MA study) of this symptom. METHODS: A Team for Pain Management (TPM) represented by radiation oncologist and anesthetist weekly provided consultations to patient presenting cancer pain. TPM prospectively reported epidemiologic, symptomatic, and pharmacological data. TPM modified pain therapy and indicated antalgic radiotherapy. Patients were evaluated at baseline and after 4 weeks after intervention. RESULTS: From November 2015 to April 2016, 65 patients were evaluated by TPM. At the baseline, 18 patients (27.7%) were undertreated (i.e., receiving inadequate pain management); furthermore, 27 patients (41.5%) despite receiving strong opioids had uncontrolled pain. After 4 weeks from intervention, undertreated patients were reduced to 1.53%. For those patients undergone to radiotherapy, response at 34 weeks was scored as follows: complete response 28.8%, partial response 46.7%, pain progression 0.95%, indeterminate response 23.8%. CONCLUSIONS: A multidisciplinary Team for Pain Management improved the clinical management, optimizing pain control and increasing adequacy of pharmacological management. The TPM intervention seems particularly worth for patients presenting specific features including BTcP, neuropathic pain, severe pain due to bone metastases, and any potential candidate to radiotherapy. Larger series and QoL questionnaires are required to confirm these results.

Could a vitamin D deficiency cause a combined long-term FEV1 and bone mineral density deterioration in female asthmatics?

OBJECTIVES: We already know that asthma is associated to osteoporosis/osteopenia and characterized by an accelerated lung function decline. Our study aimed at assessing whether lung function decline and bone mineral density (BMD) deterioration in time were associated in a group of female long-standing asthmatics. We also tried to understand whether these two aspects were related to ICS treatment and vitamin D levels. METHODS: 35 female asthmatics were retrospectively analysed. Results of methacholine challenge test at asthma onset, FEV1%, bone density scan at moment of recruitment and after at least 5years later were considered. RESULTS: A significant positive relationship between femoral-t-scores changes and FEV1 decline was found after a median follow-up time of 7 [6-9] years (r=0.43;p=0.04). Femoral-t-score variations and vitamin D values were also significantly related (r=0.669;p=0.024). Furthermore, we found that FEV1 decline was worse in subjects with lower vitamin D levels (-57.5[-80.4-35.9]ml/year), compared to those with normal vitamin D rates (12[-16-23.6]ml/year;p=0.055). Femoral/vertebral t-score changes, as well as FEV1, decline were not associated to the use of medium/high ICS doses when compared to subjects treated with low ICS dosages. CONCLUSIONS: FEV ¹ decline and BMD deterioration in time observed in a group of female asthmatics were associated; low vitamin D levels may be the link.

Squamous cell carcinoma of the rectum: The treatment paradigm.

PURPOSE: This study was planned to clarify the optimal treatment for squamous cell carcinoma of the rectum, an histological entity extremely rare. METHODS: Ten patients with histologically proven squamous cell carcinoma of the rectum were treated with concomitant radiochemotherapy. Radiation therapy was delivered with a 3Dconformational multiple field technique to a dose ranging from 45 to 76.5 Gy, with 6-15 MV energy photons. Chemotherapy consisted of an antimetabolite drug in association with mitomycin C or oxaliplatin. Overall survival and disease free survival were considered in months from the end of the concomitant treatment. RESULTS: All patients completed programmed radiochemotherapy treatment but two patients were excluded to the analysis. Six patients (75%) presented negative biopsy 6 months after the end of radiochemotherapy. Seven patients (87.5%) showed a tumour regression after initial treatment. Only 1 patient underwent salvage surgery. Considering a mean follow-up of 41.75 months, 7 patients are still disease free survivors. Only 1 patient developed local recurrence at 6 months and he died 14 months after abdomino-perineal resection. CONCLUSION: Primary radio chemotherapy, with a curative intent, could be considered the treatment modality of choice for squamous carcinoma of the rectum.

Stereotactic radiosurgery (SRS) with volumetric modulated arc therapy (VMAT): interim results of a multi-arm phase I trial (DESTROY-2).

AIMS: To present the interim results of a phase I trial on stereotactic radiosurgery (SRS) delivered using volumetric modulated arc therapy (VMAT) in patients with primary or metastatic tumours in different extracranial sites. MATERIALS AND METHODS: Patients were enrolled in different arms according to tumour site and clinical stage, and sequentially assigned to a given dose level. Acute toxicity, tumour response and early local control were investigated and reported. RESULTS: One hundred lesions in 65 consecutive patients (male/female: 30/35, median age: 66 years; range: 40-89) were treated. Of these 100 lesions, 21 were primary or metastatic lung tumours, 24 were liver metastases, 30 were bone metastases, 24 were nodal metastases and one was a primary vulvar melanoma. The prescribed dose ranged from 12 (BED(2Gy,α/ß:10) = 26.4 Gy) to 28 Gy (BED(2Gy,α/ß:10) = 106.4 Gy) to the planning target volume. Twenty-one patients (32.3%) experienced grade 1-2 acute toxicity, which was grade 2 in only two cases. The overall response rate based on computed tomography/magnetic resonance imaging was 52% (95% confidence interval 40.1-63.2%) and based on positron emission tomography scan was 90% (95% confidence interval 76.2-96.4%). As of November 2013, the median duration of follow-up was 11 months (range = 1-38). Recurrence/progression within the SRS-VMAT treated field was observed in nine patients (total lesions = 18): the inside SRS-VMAT field local control expressed on a per lesion basis was 87.8% at 12 months and 71.9% at 24 months. CONCLUSIONS: The maximum tolerable dose has not yet been reached in any study arm. SRS-VMAT resulted in positive early clinical results in terms of tumour response, local control rate and acute toxicity.

Quasi real time in vivo dosimetry for VMAT.

PURPOSE: Results about the feasibility of a method for quasi real time in vivo dosimetry (IVD) at the isocenter point for volumetric modulated arc therapy (VMAT) are here reported. The method is based on correlations between the EPID signal and the dose on the beam central axis. Moreover, the γ-analysis of EPID images was adopted to verify off-axis reproducibility of fractionated plan delivery. METHODS: An algorithm to reconstruct in vivo the isocenter dose, D(iso), for RapidArc treatments has been developed. 20 VMAT plans, optimized with two opposite arcs, for prostate, pancreas, and head treatments have been delivered by a Varian linac both to a conic PMMA phantom with elliptical section and to patients. The ratios R between reconstructed D(iso) and the planned doses were determined for phantom and patient irradiations adopting an acceptance criterion of ±5%. In total, 40 phantom checks and 400 patient checks were analyzed. Moreover, 3% and 3 mm criteria were adopted for portal image γ-analysis to assess patient irradiation reproducibility. RESULTS: The average ratio R, between reconstructed and planned doses for the PMMA phantom irradiations was equal to 1.007 ± 0.024. When the IVD method was applied to the 20 patients, the average R ratio was equal to 1.003 ± 0.017 and 96% of the tests were within the acceptance criteria. The portal image γ-analysis supplied 88% of the tests within the pass rates γ(mean) ≤ 0.4 and P(γ<1) ≥ 98%. All the warnings were understood comparing the CT and the cone beam CT images and in one case a patient's setup error was detected and corrected for the successive fractions. CONCLUSIONS: This preliminary experience suggests that the method is able to detect dosimetric errors in quasi real time at the end of the therapy session. The authors intend to extend this procedure to other pathologies with the integration of in-room imaging verification by cone beam CT.

Low-dose fractionated radiotherapy and concomitant chemotherapy for recurrent or progressive glioblastoma: final report of a pilot study.

BACKGROUND: Evaluated in this study were the feasibility and the efficacy of concurrent low dose fractionated radiotherapy (LD-FRT) and chemotherapy as palliative treatment for recurrent/progressive glioblastoma multiforme (GBM). PATIENTS AND METHODS: Eligible patients had recurrent or progressive GBM, Karnofsky performance status ≥ 70, prior surgery, and standard radiochemotherapy treatment. Recurrence/progression disease during temozolomide (TMZ) received cisplatin (CDDP; 30 mg/m(2) on days 1, 8, 15), fotemustine (FTM; 40 mg/m(2) on days 2, 9, 16), and concurrent LD-FRT (0.3 Gy twice daily); recurrence/progression after 4 months from the end of adjuvant TMZ were treated by TMZ (150/200 mg/m(2) on days 1-5) concomitant with LD-FRT (0.4 Gy twice daily). Primary endpoints were safety and toxicity. RESULTS: A total of 32 patients were enrolled. Hematologic toxicity G1-2 was observed in 18.7 % of patients and G3-4 in 9.4 %. One patient (3.1 %) had complete response, 3 (9.4 %) had partial response, 8 (25 %) had stable disease for at least 8 weeks, while 20 patients (62.5 %) experienced progressive disease. The clinical benefit was 37.5 %. Median progression-free survival (PFS) and overall survival (OS) were 5 and 8 months, respectively. Survival rate at 12 months was of 27.8 %. CONCLUSION: LD-FRT and chemotherapy for recurrent/progressive GBM have a good toxicity profile and clinical outcomes, even though further investigation of this novel palliative treatment approach is warranted.

Concurrent and adjuvant temozolomide-based chemoradiotherapy schedules for glioblastoma. Hypotheses based on two prospective phase II trials.

AIM: To investigate the impact of nonstandard concomitant temozolomide (TMZ) administration in two prospective phase II studies for glioblastoma (GBM). PATIENTS AND METHODS: From October 2000 to June 2008, 104 patients were enrolled in two studies: 25 in RT-TMZ-10.00 and 79 in RT-TMZ-01.04. Adjuvant radiotherapy (RT) was used with a total dose of 59.4 Gy (1.8 Gy/day). Patients received concomitant TMZ (75 mg/m(2)/day) from Monday to Friday during the first and last weeks of RT in the RT-TMZ-10.00 study and from Monday to Friday during all weeks of RT in the RT-TMZ-01.04 trial. Adjuvant TMZ (200 mg/m(2)) was administered for 5 days every 28 days. RESULTS: Median progression-free (PFS) and overall survival (OS) were 9 and 16 months, respectively, with no significant difference between the two groups (p = 0.5 and 0.14, respectively). The 2- and 5-year OS rates were 32 and 3 %, respectively, and similar to those observed with standard treatment regimens. CONCLUSION: Our data support the hypothesis that adjuvant TMZ is more important than concomitant chemotherapy (CH) and that RT is the more important element of the concomitant treatment schedule.

[The role of Proxelan in the treatment of chronic prostatitis. Results of a randomized trial]. / Ruolo di Proxelan nel trattamento delle prostatitit croniche. Risultati di un trial randomizzato.

AIM: Inflammatory diseases of the prostate are one of the most difficult problems to manage in the fertile male aged between 20 and 50. Antibiotics are the gold standard for the treatment of both bacterial (category II-NIH) and non bacterial prostatitis (category III-NIH). However, antibiotics need to be associated with other therapies focused on reducing symptoms and providing a better quality of life. In the present study we sought to test the effectiveness of antibiotics and the medical device Proxelan suppositories taken together. METHODS: Starting in January 2011, we conducted a randomized controlled trial involving 60 subjects with bacterial and non bacterial chronic prostatitis, who were divided into two groups. Subjects allocated in group A received only antibiotics for 28 days; subjects in group B received antibiotics + Proxelan, for 28 days as well. Before randomization all subjects underwent Meares-Stamey test, IPSS and NIH-CPSI questionnairs. All of those were repeated 60 and 120 days after randomization. Microbiological and clinical efficacy were compared using specific statistical analyses. RESULTS: Data were obtained from 29 subjects allocated in group A and 31 in group B. Minor side effects were observed which did not cause study interruption in any case. Of the total population, 68,3% resulted positive to the Meares-Stamey test at study start. Proxelan was not better than antibiotics alone under a microbiological point of view (OR)=0.9; (IR) 0.3-2.8; P=0.46. According to the answers provided at the NIH-CPSI questionnaire, subjects in the group B obtained a better score compared to group A, either after 2 months (OR:2.8; 95%IC 1.2-4.1; P=0.017) and after 4 months (OR:1.67; 95%IC 0.9-2.9; P=0.04). With regards to the IPSS questionnaire, 2 months after treatment start, subjects in the group A had a probability of having urinary symptoms 2 times higher compared to subjects in group B (OR:1.9; 95%IC 1.0-3.5; P=0.028). Although Proxelan seems to improve IPSS also after 4 months, the difference does not reach the level of statistical significance. CONCLUSION: Compared to antibiotics alone, the combination of antibiotics and Proxelan improve both symptoms associated to chronic prostatitis and urinary symptoms, however microbiological results are not different. Future studies may be required to confirm our results and to explain the mechanism of action of Proxelan.

Nutritional counselling and oral nutritional supplements in head and neck cancer patients undergoing chemoradiotherapy.

BACKGROUND: The role of nutritional counselling (NC) with or without oral nutritional supplements (ONS) in patients receiving chemoradiotherapy (CRT) for head and neck cancer (HNC) still remains to be clearly defined, particularly with regard to CRT-related toxicity. METHODS: Patients undergoing CRT for HNC received NC by the dietitian within the first 4 days of radiotherapy and weekly for the course of radiotherapy (approximately 6 weeks). A weekly supply of oral nutrition supplements [1560 kJ (373 kcal) per 100 g] for up to 3 months was provided to all patients. RESULTS: Twenty-one patients completed CRT. Mucositis G3 developed in seven (33.3%) patients, whereas mucositis G4 was absent. Dysphagia was present before the start of treatment in four patients. In the remaining 17 patients, dysphagia G3 developed during/at the end of treatment in five cases. The percentage of patients interrupting anti-neoplastic treatment for was 28% for ≥6 days, 28% for 3-5 days and 44% for 0-2 days. Mucositis G3 frequency was lower in patients with a baseline body mass index (BMI, kg m(-2) ) ≥25 (two out of 12; 16.6%) than in patients with BMI <25 (five out of nine; 55.5%) (P = 0.161) and in patients with a baseline mid arm circumference >30 cm than in those with a mid arm circumference in the range 28.1-30 cm and <28 cm, and higher in patients with a greater weight loss and a greater reduction of serum albumin and mid arm circumference. CONCLUSIONS: Nutritional counselling and ONS are associated with relatively low CRT-related toxicity and with mild deterioration of nutritional parameters.

The role of radiotherapy in adult medulloblastoma: long-term single-institution experience and a review of the literature.

Medulloblastoma (MB) occurs infrequently in adult patients and standard treatment is still controversial. We report our long-term, single-institution experience of adult MB and a review of the literature. We analysed adult patients with histologically proved MB treated by postoperative radiotherapy. Primary endpoints were local control (LC), disease-free survival (DFS), and overall survival (OS). Acute toxicity was reported according to CTC-NCI score vers. 3.0 and specific neuropsychological assessment analysis was performed to define late brain toxicity. From 1990-2008, 13 patients were treated by craniospinal (CSI, 12/13) or cranial irradiation (1/13, because of bad clinical conditions). Median follow up was 101 months (64-218). Complete radiological response was observed in 12/13 patients and a partial response in 1/13. Ten-year LC, OS, and DFS were 91, 76, and 84%, respectively. Two patients died because of local and spinal progression after 13 and 62 months. Acute G3 haematological toxicity (RTOG score) was observed for one patient only. The neuropsychological analysis did not reveal late toxicity related to brain radiotherapy. This experience confirms the efficacy and safety of radiotherapy in adult MB patients, resulting in very interesting 10-year LC and OS.

[Epidemiology of femoral neck fractures in Puglia (Italy): an analysis of existing data]. / Epidemiologia delle fratture del collo del femore in Puglia attraverso l'analisi dei dati correnti.

The aim of this study was to describe the epidemiology of femoral neck fractures in Puglia (Italy) by analysing hospital discharge records from 1998 to 2005 and mortality data from 1998 to 2003. In total, 41,354 admissions for femoral neck fractures were recorded, 75% of which in females. The mean age of patients was 78 years (73 in males, 79 in females). Approximately 70% of patients below 50 years of age were male, while above age 50, only 23% of patients were male. Yearly admission rates increased from 1998 to 2005. Mortality records recorded 1,031 deaths due to femoral neck fracture with a decreasing trend in mortality rates in the years considered. Fractures in males were most commonly associated with work related accidents and motor vehicle accidents. In females most fractures were related to home accidents. These results may be used to guide prevention strategies.

[The outpatient care in the Latium region (Italy) in 2001]. / L'assistenza specialistica ambulatoriale nella regione Lazio nell'anno 2001.

The Region of Latium has been operating an Outpatient Care Information System (SIAS) since 1997 to monitor the supply of outpatient care in a territory with a population of over five million. The present work has the aim of describing the outpatient care in the region, in terms of number of facilities involved by category (public and private, operating in the regional public health system) and volume of procedures rendered to residents in 2001. Of the 971 outpatient facilities operating in hospitals and elsewhere--37% state managed and 67% private--distributed in a non-uniform manner throughout the region, the majority is concentrated in the city of Rome, which by itself accounts for 49% of its total amount of facilities, and in a lesser measure in the other provincial capitals (Viterbo, Rieti, Frosinone, Latina). In 2001, 71 million procedures were performed, comprising 17 million prescriptions, for an economic value of over 400 million Euros. The three specialties of greatest use were Lab Analysis, Physical Therapy and Rehabilitation, and Radiology, making up 88% of the total outpatient procedures performed within the precinct of the regional health service, in respective measures of 57%, 27%, and 4%. It is noted that the public facilities are prevalently polyspecialistic while a great number of private facilities are monospecialistic and perform procedures almost exclusively (96%) in the three specialties of greatest use. The other specialties which receive notable use are Cardiology, Eye Care, Orthopedics and Neurology. In general, the greater the number of facilities there are in either the public or private sector, the greater the level of activity in terms of procedures performed, with the exception of the area of Physical Therapy and Rehabilitation where the correlation is inversely proportioned; in fact, for this specialty the public facilities, which are represented in a much greater number throughout the region, supply only 7% of the volume of activity.

Locoregional pain treatment. Troubles and prospectives: antalgic radiotherapy.

Pain control in patients with cancer represents a significant aspect of radiation therapy practice. Radiation therapy is one of the most effective, and often the only, therapeutic option to relieve pain caused by nerve compression or infiltration by malignant tumor, pain from liver and bony metastases and it provides also successful palliation of dysphagia caused by oesophageal carcinoma and of pain due to pancreatic cancer. Various instruments are avaliable for pain evaluation but a valid methodology to assess the pain status in the patient with cronic cancer pain is still an important clinical problem. In this complex and wide scene this contribution wants to confirm the role of radiotherapy in cancer pain control, in paricular in bone metastases, and to involve the patient himself in the survey of radiation treatement response by a subjective evaluation of bone pain, elaborating a reliable and valid unidimensional method by which recording the self-rating of the patient's sensation. Materials and Methods For the subjective evaluation of pain caused by bone metastases we used an application form with which drawing information in the course of time in terms of: response to the treatment, duration of symptom relief and quality of life. Results Considering as cut-off a dose of 30 Gy, which is commonly considered the conventional treatment for bone metastases, the partial and complete response were, respectively, of 54% and 30% in the patients treated with dose higher than or equal to 30 Gy, and 60% and 20% in the ones treated with doses lower than 30 Gy. In the whole, in 84 patients, the global response was of 82%, in accordance with literature. Conclusion In this retrospective study, the analysis of patient's subjective experience confirmed the effectiveness of radiotherapy in reducing pain caused by bone metastases and in improving quality of life of the patient himself. Given the conflicting opinions on low-dose short-course radiotherapy versus prolonged or higher dose schedules on initial pain relief, we are going to define categories of homogenous patients on whom starting treatment schedules with the aim or of palliation of the symptom or of the functional restitutio, on the base of the expectation and the quality of life.

Intraoperative radiotherapy: current thinking.

Intraoperative radiotherapy (IORT) refers to the delivery of irradiation at surgery. A large single dose of irradiation is delivered to a surgically defined area, while uninvolved and dose-limiting tissues are displaced, the final goal of IORT being enhanced locoregional tumour control. IORT is used in most modern protocol studies as a boost radiation component of multidisciplinary treatment approaches. More recently, high activity radiation sources or mobile operating room treatment machines are used to facilitate the IORT procedure. Clinical experiences have shown that IORT may improve local control and disease-free survival, especially when used in adjuvant setting, combined with external beam irradiation in some neoplasms such as cancer of the stomach, pancreas, colorectum, and soft tissue sarcoma.

Lamivudine treatment failure in preventing fatal outcome of de novo severe acute hepatitis B in patients with haematological diseases.

BACKGROUND: Patients with malignant haematological diseases administered or no longer receiving immunosuppressive therapy are at high risk of reactivation or de novo hepatitis B infection and fulminant hepatitis. Despite promising results in the treatment of chronic hepatitis and its use in selected patients with acute hepatitis B, there is no consensus on lamivudine treatment in severe acute hepatitis portending a fatal clinical outcome. CASE REPORTS: Of the ten patients with malignant haematological disorders who became infected with the same strain of hepatitis B virus during hospitalisation in a haematology ward, five received lamivudine (and in some cases, ganciclovir and famciclovir). The other patients received only supportive therapy, since deteriorating clinical conditions hampered specific treatment efforts. Eight patients died from acute liver failure and one from a fatal course of the haematological disease; one had a favourable outcome from the therapy. There was no significant difference in terms of survival between the treated and untreated patients. CONCLUSIONS: Although lamivudine has proved promising in the therapy of chronic hepatitis B and of recurrent hepatitis after liver transplantation, its use in de novo severe acute hepatitis should be investigated further, particularly in immunocompromised patients.

Radiotherapy versus follow-up in the treatment of pathological stage Ia and Ib non-small cell lung cancer. Early stopped analysis of a randomized controlled study.

OBJECTIVE: This is an analysis of a randomized controlled clinical trial planned to evaluate the effects of adjuvant radiotherapy (AR) on the local recurrence rate in patients with non-small cell lung cancer (NSCLC) with pathological stage (pStage) Ia (pT1N0) and Ib (pT2N0). The effects of AR on the long-term survival have also been marginally evaluated. MATERIALS AND METHODS: This clinical trial was planned with the hypothesis that AR on pStage Ia and Ib, R0 NSCLCs was effective on local recurrence rate. From July 1989 through March 1997, 104 patients with NSCLC who presented with pStage Ia and Ib have been observed and treated and entered the study. Male/female ratio was 91:13; the mean age was 62 years (range 41-75 years). All patients underwent major pulmonary resection and homolateral standard hilar and mediastinal lymph node dissection. pStage was T1N0 in 29 and T2N0 in 75 cases. Patients have been randomized 'by chance' into two groups (G1 and G2). G1 received radiotherapy, G2 did not receive any adjuvant treatment. Fifty-two patients entered G1 and 52 entered G2. RESULTS: Post-operative mortality was nil. Seven patients have been excluded from the study (four in G1 and three in G2), due to incomplete follow-up data. We do not report any radiotherapy-related complication or deterioration of lung function. The treatment effect on the local recurrence rate demonstrated a clearly significant protective effect of the AR. No statistically significant difference was found from the comparison of the 5-year survival rate of the treated (83%) versus untreated (70%) patients. No detrimental effect of the radiotherapy has been assessed. CONCLUSIONS: AR in the treatment of pStage Ia and Ib NSCLC has been well tolerated and had a significant relative effect on the local recurrence rate but did not significantly modify overall survival even if a positive trend in the group of treated patients is reported.

Reduction in mortality with availability of antiretroviral therapy for children with perinatal HIV-1 infection. Italian Register for HIV Infection in Children and the Italian National AIDS Registry.

CONTEXT: Since the introduction of combined antiretroviral therapy, mortality rates in adults with human immunodeficiency virus type 1 (HIV-1) infection have decreased. However, little information is available outside the setting of controlled trials on survival of perinatally HIV-infected children treated with antiretroviral therapy. OBJECTIVE: To assess effect of availability of antiretroviral therapy on decreasing mortality in perinatally HIV-infected children. DESIGN: Population-based, multicenter longitudinal study involving data collected by the Italian Register for HIV Infection in Children. SETTING: A network of 106 pediatric clinical centers. SUBJECTS: A total of 1142 children born between November 1980 and December 1997 with perinatally acquired HIV infection with a median follow-up of 5.9 years. MAIN OUTCOME MEASURE: Time to HIV-related death calculated for birth cohort and calendar period and grouped by distribution of predominant type of antiretroviral therapy administered over time. RESULTS: Survival was longer in the 1996-1997 birth cohort (crude relative hazard [RH] of death, 0.39; 95% confidence interval [CI], 0.15-0.96) and 1996-1998 calendar period (crude RH of death, 0.65; 95% CI, 0.45-0.95) than in birth cohort and calendar period 1980-1995, but not when adjusted for maternal antiretroviral treatment during pregnancy and clinical condition at time of delivery, gestational age, and birth weight (adjusted RH of death, 0.55; 95% CI, 0.20-1.50, for birth cohort; and adjusted RH of death, 0.71, 95% CI, 0.43-1.16, for calendar period). In a multivariate model with 1980-1995 as comparison, the 1996-1997 birth cohort had an RH of 0.57 (95% CI, 0.22-1.47; P=.27) but RH for calendar period 1996-1998 was 0.63 (95% CI, 0.47-0.85; P<. 01). When the effects of birth cohort, calendar period, and type of antiretroviral therapy were evaluated simultaneously in the same model, the RH of death was not significantly different from 1.0 for the 1996-1997 birth cohort (P=.19) and calendar period 1996-1998 (P=. 83) suggesting a causal relationship between decreased risk of death and use of combination therapy. The RH of death in children receiving monotherapy or double or triple combination therapy was 0. 77 (95% CI, 0.55-1.08), 0.70 (95% CI, 0.42-1.17), and 0.29 (95% CI, 0.13-0.67), respectively, vs no antiretroviral therapy. CONCLUSION: Survival of perinatally HIV-infected children improved in 1996-1998 as a result of the introduction of combined antiretroviral therapies. JAMA. 2000;284:190-197