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.

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.

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.

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.

Research trends in the treatment of colorectal cancer.

Colorectal carcinoma ranks second in incidence after lung cancer in males and breast carcinoma in females. Within the clinical research on this tumor, new molecules of antineoplastic agents and new combined modality treatments have been introduced. From the examination of ongoing protocols some trends can be identified: the interest in immunotherapy and genetic therapy, frequently tested in combination with chemotherapy; the effort at the optimization of the administration of antineoplastic agents in the most common sites of metastatic lesions by hepatic or intraperitoneal infusion; the trend to a more aggressive treatment of metastastatic lesions with hyperthermia and cryoablation as well with the combination of systemic therapy and surgery. As far as radiotherapy is concerned, the main goals of clinical research seem represented by the need to optimize combined modality therapy in T3-4 rectal carcinoma both in terms of pre- and postoperative radiotherapy timing as well as of the combination with adjuvant chemotherapy. There is a growing interest in new drugs which in the future may replace the conventional 5-fluorouracil in concurrent chemoradiation.

Advances in the treatment of lung cancer: economic and organizational aspects.

The organizational optimization in radiotherapy tends to a correct balance of quality of service and containment of health care expenditure; this goal is necessarily correlated with the real potentialities available to each center while considering the possible clinical benefits for the patient. In lung cancer, outcomes achieved with radiation therapy are encouraging in terms of local control and survival when treatment is performed with the available modern technology whose costs from an exclusively economic analysis are shown to be still quite high. In an assessment focused on clinical outcomes, better local control, higher survival and improved quality of life represent tangible benefits: this has a positive impact on community costs and may represent a high priority goal for health care providers, yielding a benefit that can be quantified with the most recent analyses of health care economy.

Radiotherapy, local control and survival in brain tumors.

High grade glial brain tumors and brain metastases are a complex subject with still unsatisfactory therapeutic results for the frequent absence of early and precise diagnosis as well as for the limited therapeutic interval between the tumor and presumed healthy tissues. The therapeutic problems of cellular hypoxia, the rapid recovery of sublethal damage for neoplastic cells, the rapid regrowth, have led to a number of efforts to deliver the dose of radiotherapy in various associations. The constant technological trend to increase the high dose gradient to the peripheral tumor, is reported.

Radiotherapy, local control and survival in lung cancer.

Better local control in locally advanced IIIA-B non small cell lung cancer, not considered for surgery, can be achieved through therapy intensification with non conventional fractionation of radiation dose, concomitant boost to the tumor volume, conformal therapy and combined modality therapy. All these procedures tend to produce an improved response, which, if stable in time, may also improve local control and survival. The reported experiences define a positive and encouraging trend on which new guidelines for a more suitable definition of standard therapies for the disease can be modulated.

[Epoetin alfa in radiotherapy]. / Epoetina alfa in radioterapia.

Sixty per cent of oncologic patients need radiation therapy for cure or palliation. In fact, in most neoplastic diseases, a better local control positively impacts on disease-free survival and overall survival. The efficacy of radiotherapy depends on several factors: while some are tumor-related, others are host-related. Radiobiological phenomena are also important: ionizing radiation is responsible for cell damage (double rupture of DNA chains), mostly an indirect mechanism with the formation of free radicals. Their toxic action is enhanced by the oxygen partial pressure at the cellular level. A number of studies have confirmed that good tissue oxygenation is a function of a high hemoglobin level in the peripheral blood (Hb > or = 13 g/dL). Unfortunately, these values are rarely present in oncologic patients due to the disease-related toxicosis as well as to the therapy induced hematologic toxicity. The treatment of anemia is free of risk for the recent developments in technology which with gene cloning and the technique of recombinant DNA has allowed the production of human recombinant erythropoietin. Erythropoietin is produced by the interstitial cells of renal tubules in response to hypoxia. It prevents apoptosis and promotes erythroid proliferation and differentiation with consequent reticulocyte release and hemoglobin synthesis. It is not completely understood whether the efficacy of radiotherapy depends on hemoglobin values present at the start of irradiation (often less than 12-13 g/dL) or on the higher ones observed during and at the end of radiotherapy. Therefore, preventive systemic erythropoietin therapy in non anemic patients in terms of costs/benefits is at present non sustainable. To the contrary, in patients undergoing radiotherapy to extended fields or aggressive multimodal treatments, for the higher risk of anemia, the early use of this treatment can be hypothesized in case of initial anemia to improve therapy compliance and prevent negative conditioning of results. Keeping in mind that grade 1 minimum toxicity for red cells, according to the Radiation Therapy Oncology Group (RTOG) is equal to 11 gHb/dL we think that this value can be considered as cutoff to start erythropoietin therapy.