Variability in axillary lymph node delineation for breast cancer radiotherapy in presence of guidelines on a multi-institutional platform.

AIM: To quantify the variability between radiation oncologists (ROs) when outlining axillary nodes in breast cancer. MATERIAL AND METHODS: For each participating center, three ROs with different levels of expertise, i.e., junior (J), senior (S) and expert (E), contoured axillary nodal levels (L1, L2, L3 and L4) on the CT images of three different patients (P) of an increasing degree of anatomical complexity (from P1 to P2 to P3), according to contouring guidelines. Consensus contours were generated using the simultaneous truth and performance level estimation (STAPLE) method. RESULTS: Fifteen centers and 42 ROs participated. Overall, the median Dice similarity coefficient was 0.66. Statistically significant differences were observed according to the level of expertise (better agreement for J and E, worse for S); the axillary level (better agreement for L1 and L4, worse for L3); the patient (better agreement for P1, worse for P3). Statistically significant differences in contouring were found in 18% of the inter-center comparison. Less than a half of the centers could claim to have a good agreement between the internal ROs. CONCLUSIONS: The overall intra-institute and inter-institute agreement was moderate. Central lymph-node levels were the most critical and variability increased as the complexity of the patient's anatomy increased. These findings might have an effect on the interpretation of results from multicenter and even mono-institute studies.

The COVID-19 Stress Perceived on Social Distance and Gender-Based Implications.

The COVID-19 pandemic is an unprecedented event entailing long-term consequences on population health and welfare. Those who contracted the coronavirus may have suffered from both physical and mental health issues that unfold the need for tailored intervention strategies. Hence, our study aims to investigate the psychological and social consequences of COVID-19 on a sample of 86 participants, encompassing 43 patients (clinical group; 25 women; mean age = 50.4 ± 10.1 years) recruited from Bari University Hospital, 19 of whom were hospitalized due to the disease. The remaining 43 were individuals not fallen ill with COVID-19 to date (control group; 25 women; mean age = 50.4 ± 10.1 years). The investigation yielded significant gender differences in post-traumatic stress symptoms, depression, and representation of interpersonal distance (IPD), evaluated through the IES-R, the BDI-II, and the IVAS task, respectively. This pattern of results was not replicated in the control group. In general, participants who reported having experienced the most intense post-traumatic symptoms also presented a greater mood deflection and, more specifically, within the clinical group women obtained the highest scores on both scales. Women reported higher IES-R and BDI-II scores compared to men, that could indicate that women who have contracted COVID-19 are more exposed to post-traumatic and depressive symptoms. Our results also showed a significant effect of COVID-19 on IPD with a tendency of disease-experienced individuals to increase their preferred IPD from adults, children, and elderly people. Regarding gender differences in mood and proxemic behavior, a correlation between depressive symptoms and probable PTSD and a further correlation between probable PTSD and greater IPD were found in women from both clinical and control group. Overall, these findings might contribute to a better understanding of gender-based implications of the current pandemic on mental health, also leading to the development of integrated yet personalized intervention strategies.

Bioelectrical Impedance Vector Analysis for Nutritional Status Assessment in Systemic Sclerosis and Association With Disease Characteristics.

OBJECTIVE: To use bioelectrical impedance vector analysis (BIVA) in a cohort of patients with systemic sclerosis (SSc) in order to assess their nutritional status in comparison to other groups of patients and to find any correlation with clinical characteristics and outcome of the disease. METHODS: We retrospectively collected data from 50 SSc patients who underwent BIVA for clinical suspicion of malnutrition and compared them with patients affected by other chronic autoimmune rheumatic diseases (OCAD, n = 27) and those who were only symptomatic of malnutrition but without autoimmune features (n = 15), and with 50 healthy controls (HC). RESULTS: Patients with SSc presented significantly lower values of phase angle (PhA), basal metabolic rate (BMR), and body cellular mass (BCM), and an increase in extracellular water (ECW; P < 0.01 for all) than HC; instead, there were no significant differences for BMI. No significant differences were found between SSc and OCAD. Among patients with SSc, age directly correlated with ECW (ρ = 0.342, P = 0.015) and inversely with PhA (ρ = -0.366, P = 0.009). Female sex, anemia, hypoalbuminemia, reflux, and early satiety/abdominal distension associated with relevant alterations in BIVA results. BIVA variables were significantly different when cardiopulmonary and microvascular involvement was present. Four patients died during the study: they had significantly (P ≤ 0.01) lower PhA, BMR, and BCM, with an increased ECW. CONCLUSION: BIVA, unlike BMI, allowed an accurate characterization of SSc patients at risk of malnutrition, correlating with serological malnutrition markers, with SSc-specific organ manifestations (cardiopulmonary involvement and microvascular damage), and with mortality. BIVA variables might represent a surrogate marker of damage accrual that leads to malnutrition, thus playing a leading role in the prognostic stratification of SSc patients.

A theoretical dose-escalation study based on biological effective dose in radioimmunotherapy with (90)Y-ibritumomab tiuxetan (Zevalin).

AIM: To investigate the variation in biological effective dose (BED) produced by the uncertainty in absorbed dose and radiobiological parameters in Zevalin radioimmunotherapy. METHODS: Eight patients scheduled for treatment with standard administration of (90)Y-ibritumomab tiuxetan (Zevalin) were studied. Patient-specific pretherapy dosimetry was performed by injection of (111)In-ibritumomab tiuxetan. Absorbed doses and BEDs were calculated for critical organs (COs) and tumours, assuming a 30% dose uncertainty and varying the radiobiological parameters in a reasonable range. In an activity-escalation study, BEDs for the COs were compared with the BED limits of external beam radiotherapy (EBRT) and BEDs for the tumour with the EBRT dose prescriptions. RESULTS: At standard activities, the absorbed doses per unit activity for the COs were in agreement with those in the literature. Absorbed doses to lesions were rather variable, ranging from 1.47 to 16.7 Gy/GBq. Median tumour absorbed dose to lesions in the range 80-110 g was 9.6 Gy/GBq (range 9.2-16.7 Gy/GBq), yielding a mean BED of about 12 Gy for administration of 15 MBq/kg. For the administration of the myeloablative activity of 45 MBq/kg, risk of liver toxicity in one patient would have been foreseen by the model. Considering also the dose uncertainty, the potential risk of liver toxicity in one more patient, lung toxicity in one patient, and kidney toxicity in one patient would have been suggested. The absorbed dose uncertainty was found to be the main source of uncertainty in the BED. As for radiobiological parameters, at myeloablative activities, the increase in the repair half-time for sublethally damaged tissue (T(mu)) from 0.5 h to 5 h induced more consistent increases in mean BED/BED(limit) than alpha/beta variation from 2 Gy to 5 Gy: at 53 MBq/kg, 38% for the liver, and 34% for the lungs and kidneys (about threefold higher than that obtained for the increase alpha/beta). CONCLUSION: At standard activities, absorbed doses to lesions appear to be effective, even though lower than prescribed by EBRT. At myeloablative dosages, the uncertainty associated with the absorbed doses and radiobiological parameters considerably affect BED evaluation and may account for possible "second-organ" toxicities.

Risk Perceptions and Psychological Effects During the Italian COVID-19 Emergency.

The current study provides data about the immediate risk perceptions and psychological effects of the COVID-19 pandemic among Italian participants. A sample of 980 volunteers answered a web-based survey which aimed to investigate the many facets of risk perceptions connected to COVID-19 (health, work, institutional-economy, interpersonal and psychological), and risk-related variables such as perceived knowledge, news seeking, perceived control, perceived efficacy of containment measures, and affective states. Socio-demographic characteristics were also collected. Results showed that although levels of general concern are relatively high among Italians, risk perceptions are highest with regards to the institutional-economy and work, and lowest concerning health. COVID-19 has been also estimated to be the least likely cause of death. Cognitive and affective risk-related variables contributed to explain the several risk perception domains differently. COVID-19 perceived knowledge did not affect any risk perception while the perceived control decreased health risk likelihood. The other risk-related variables amplified risk perceptions: News seeking increased work and institutional-economy risk; perceived efficacy of containment measures increased almost all perceived risks; negative affective states of fear, anger and sadness increased health risk; anxiety increased health, interpersonal and psychological risks, and uncertainty increased work, institutional-economy, interpersonal and psychological risk perceptions. Finally, positive affective states increased health risk perception. Socio-psychological implications are discussed.

Radiotherapy and chemotherapy in the conservative treatment of anal canal carcinoma.

AIM: To evaluate the feasibility of conformal radiotherapy and concurrent chemotherapy in patients with anal canal carcinoma. PATIENTS AND METHODS: Between 1990 and 2006, 83 patients affected by anal canal carcinoma were treated at the Radiotherapy Department of "La Sapienza" University of Rome. In all patients, a daily dose of 1.8 Gy, five times per week, was given for a total dose of 45 Gy for the whole pelvis (CTV1) and of 55-60 Gy for the tumor bed (CTV2). In 63 patients, chemotherapy consisted of two cycles of 5-fluorouracil (5-FU) and mitomycinC (MMC) or cisplatin delivery during the first and last week of radiotherapy. RESULTS: The median follow-up time for all patients was 56.2 months. Treatment response was considered complete in 53 patients (63.8%) and partial in 30 patients (36.1%). Local tumor relapse was observed in 13 patients (15.6%). The probability of overall survival for all patients at 5 years was 75%: 39% in patients who underwent radiotherapy alone and 85% in patients who underwent radiochemotherapy (p=0.0013). Concerning acute toxicity, 9 patients developed grade 1 skin toxicity (10.8%), 35 grade 2 (42.1%), 26 grade 3 (31.3%) and 3 grade 4 (3.6%); eleven patients had grade 2 diarrhea (14.5%) and 2 grade 3 diarrhea (2.4%). CONCLUSION: This analysis suggests that the treatment scheme employed was effective for anal sphincter preservation and local control.

Treatment outcomes and patterns of radiologic appearance after hypofractionated image-guided radiotherapy delivered with helical tomotherapy (HHT) for lung tumours.

OBJECTIVE: To evaluate treatment outcomes and patterns of CT lung injury after hypofractionated image-guided radiotherapy delivered with helical tomotherapy (HHT) in a series of inoperable lung lesions. METHODS: 68 patients who were medically inoperable (69 lesions) without evidence of viable extrathoracic disease were included. Dose prescription was driven by tumour location (hilar/pericentral vs peripheral) and/or target volume. 52% of the lesions received a biological equivalent dose (BED10) ≥100 Gy. Assessment of tumour response was based on the Response Evaluation Criteria in Solid Tumours 1.1 criteria coupled with fluorine-18 fludeoxyglucose/positron emission tomography-CT. Toxicity monitoring was focused on treatment-related pulmonary adverse events according to the Common Terminology Criteria for Adverse Events v. 4.0. Acute and late events were classified as radiation pneumonitis (RP) and radiation fibrosis (RF), respectively. Survival curves were calculated using the Kaplan-Meier method. Univariate and multivariate analyses of survival were performed using the Cox proportional hazards model. RESULTS: After a median follow-up of 12 months (range, 3-31 months), no instances of ≥Grade 4 RP was documented, and clinically severe (Grade 3) RP occurred in 5.8% of the patients. 2 (3%) patients developed a late severe (≥Grade 3) symptomatic RF. No specific pattern of CT lung injury was demonstrated, in both acute and late settings. Median overall survival (OS) and progression-free survival (PFS) for the entire population were 30.8 and 14.1 months, respectively. At multivariate analysis (MVA), BED10 ≥ 100 Gy and KPS ≥ 90 emerged as significant prognostic factors for OS (p = 0.01 and p = 0.001, respectively), and BED10 ≥ 100 Gy for PFS (p = 0.02). CONCLUSION: Our findings show that HHT adjusted for tumour location and/or target volume is an effective treatment with an acceptable toxicity profile in patients who are medically inoperable with lung tumours and is not associated with a specific pattern of lung injury. Therefore, it can represent a viable option when conventional stereotactic ablative radiotherapy facilities are not available. Advances in knowledge: The present study is among the largest series addressing the role of HHT for inoperable lung tumours. This technique is safe and effective and is not associated with a specific pattern of lung injury, at least at early and average time points.

Stereotactic body radiation therapy salvage reirradiation of radiorecurrent prostatic carcinoma relapsed in the prostatic bed.

A 67-year-old man presented with a slow increase of prostate-specific antigen value after radical prostatectomy and postoperative radiotherapy for prostate cancer. The patient had received 3D conformal radiotherapy to a total dose of 66 Gy in 33 fractions of 2 Gy each on the prostatic bed. Three years later, a macroscopic local failure was diagnosed at the apical region. The patient could not receive androgenic deprivation therapy or other types of treatment owing to comorbid conditions. Thus, stereotactic body radiation therapy with helical image-guided tomotherapy was administered. The total dose was 30 Gy in 5 consecutive fractions of 6 Gy each to the site of the local failure. The treatment was preceded by a transperineal-guided injection of a self-absorbable hydrogel into the prostatic bed, between rectum and bladder, in order to preserve the rectal wall, which already had received significant doses from the first radiation course. Radiation therapy was well-tolerated. After a follow-up period of 6 months, the patient remains healthy, and there has been no further evidence of metastatic spread or recurrence.

Moderately Escalated Hypofractionated (Chemo) Radiotherapy Delivered with Helical Intensity-Modulated Technique in Stage III Unresectable Non-Small Cell Lung Cancer.

PURPOSE: To assess clinical outcomes and toxicities in patients with stage III unresectable non-small cell lung cancer (NSCLC) treated with a moderately escalated hypofractionated radiotherapy delivered with Helical Intensity-Modulated Technique in combination with sequential or concurrent chemotherapy. MATERIALS AND METHODS: Sixty-one consecutive patients considered non-progressive after two cycles of induction chemotherapy were treated with a moderately escalated hypofractionated radiation course of 30 daily fractions of 2.25-2.28 Gy each administered in 6 weeks up to a total dose of 67.5-68.4 Gy (range, 64.5-71.3 Gy). Thirty-two received sequential RT after two more cycles (total = 4 cycles) of chemotherapy, while 29 were treated with concurrent chemo-radiation. The target was considered the gross tumor volume and the clinically proven nodal regions, without elective nodal irradiation. RESULTS: With a median follow up of 27 months (range 6-40), 1-year and 2-year OS rate for all patients was 77 and 53%, respectively, with a median survival duration of 18.6 months in the sequential group and 24.1 months in the concomitant group. No Grade ≥4 acute and late toxicity was reported. Acute Grade 3 treatment-related pneumonitis was detected in 10% of patients. Two patients, both receiving the concurrent schedule, developed a Grade 3 acute esophagitis. The overall incidence of late Grade 3 lung toxicity was 5%. No patients experienced a Grade 3 late esophageal toxicity. CONCLUSION: A moderately hypofractionated radiation course delivered with a Helical Intensity-Modulated Technique is a feasible treatment option for patients with unresectable locally advanced NSCLC receiving chemotherapy (sequentially or concurrently). Hypofractionated radiotherapy with a dedicated technique allows safely dose escalation, minimizing the effect of tumor repopulation that may occur with prolonged treatment time.

Radiotherapy for inoperable non-small cell lung cancer using helical tomotherapy.

AIM: To investigate the impact of tomotherapy on the dose delivered to the lungs and other normal tissues. MATERIAL AND METHODS: From February 2008 to May 2009, 35 patients with stage IIIA/IIIB non-small cell lung cancer were treated with helical tomotherapy at the S. Camillo-Forlanini Hospital. For our study we selected 20 patients who underwent chemotherapy followed by sequential radiotherapy. The planning target volume was delineated using planning CT scan and FDG-PET. The mean prescribed radiation dose was 67.5 Gy delivered in 30 fractions at a dose of 2.25 Gy per fraction. RESULTS: Median follow-up was 12.3 months. All patients developed acute esophageal toxicity, 15 of RTOG grade 1 and 5 of RTOG grade 2. At first follow-up 15 patients presented stable disease or partial response, 4 patients presented complete response, and 1 patient presented disease progression. CONCLUSIONS: Helical tomotherapy is useful to achieve dose-per-fraction escalation without increasing the treatment-related morbidity. Our results applying dose escalation were encouraging considering that we delivered doses that may be difficult to achieve with 3-dimensional treatments with no excessive complication rates.