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Background: and purpose: Radiation recall dermatitis is an adverse event predominantly due to systemic therapy administration after a previous radiation therapy course. Few case reports describe radiation recall dermatitis in breast cancer patients treated with postoperative radiation therapy following COVID-19 vaccination. In this study we investigated the incidence and severity of radiation recall dermatitis after COVID-19 vaccination in irradiated breast cancer patients., Methods: Patients that received at least one COVID-19 vaccination dose during the year after the end of postoperative breast radiation therapy were included in this observational monocentric study. Local symptoms occurring inside the radiation field after vaccination were patient-reported and scored according to the PRO-CTCAE questionnaire. Descriptive data of radiation recall dermatitis incidence and severity, and potential risk factors were evaluated., Results: A cohort of 361 patients with 756 administered COVID-19 vaccinations was analyzed. Breast symptoms were reported by 7.5% of patients, while radiation recall dermatitis was considered for 5.5%. The incidence of radiation recall dermatitis per single dose of vaccine was 2.6%, with a higher risk for the first dose compared to the second/third (4.4% vs 1%, p = 0.003), especially when administered within the first month after the end of irradiation (12.5% vs 2.2%, p = 0.0004). Local symptoms were generally self-limited and a few cases required anti-inflammatory drugs., Conclusions: Radiation recall dermatitis is an uncommon but not rare phenomenon in breast cancer patients that received COVID-19 vaccination within one year after breast irradiation. However, symptoms severity were generally low/mild and reversible. These findings can be useful for patient counseling., Competing Interests: Declaration of competing interest The authors Vinante L., Caroli A., Bertini F., Relevant A., Giroldi A., Marson M., Franchin G., Muraro E., Brisotto G., Steffan A., Baboci L. disclosed no potential conflicts of interest., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: To apply the German Hodgkin Study Group (GHSG) risk model in patients with recurrent/refractory Hodgkin lymphoma receiving involved-field radiotherapy after autologous stem cell transplantation., Material and Methods: The study consisted in the retrospective analysis of 30 consecutive patients with recurrent/refractory Hodgkin lymphoma who received involved-field radiotherapy after autologous stem cell transplantation. Our policy was of adding involved-field radiotherapy for patients with positive PET scan before autologous stem cell transplantation (23 out of 30 patients, 77%), and/or irradiating sites of bulky disease at relapse (11 out of 30 patients, 37%). Patients were stratified into four risk groups according to the presence of the five clinical risk factors identified by the GHSG; (1) stage IV disease; (2) time to relapse≤3 months; (3) ECOG-PS≥1; (4) bulk≥5cm; and (5) inadequate response to salvage chemotherapy., Results: The median interval from autologous stem cell transplantation to involved-field radiotherapy was 3 months (range, 1-7 months), and the median involved-field radiotherapy dose was 35Gy (range, 12-40Gy). At a median follow-up of 35 months (range, 1-132 months), the 2-year progression-free survival in the entire series was 60%. When examining the four different GHSG risk groups, the progression-free survival rate at 2 years was 86%, 83%, 50%, and 36% for patients with score=0, score=1, score=2, and score=3 to 5, respectively (P=0,01). Among the 12 patients havingat leastthree risk factors who underwent thoracic involved-field radiotherapy, three (25%) developed pneumonitis., Conclusion: The adoption of the GHSG risk model at the time of recurrence/progression is a useful prognostic tool to select patients with Hodgkin lymphoma for consolidative involved-field radiotherapy after autologous stem cell transplantation., (Copyright © 2019 Société française de radiothérapie oncologique (SFRO). Published by Elsevier Masson SAS. All rights reserved.)

Objectives: To evaluate the impact of time to treatment initiation (TTI) on overall survival in patients with head-and-neck squamous cell carcinoma (HNSCC)., Materials and Methods: In the period 2003-2009, 1616 HNSCC patients were diagnosed in Friuli Venezia Giulia Region, Northeastern Italy, including 462 oral, 346 oropharyngeal, 212 hypopharyngeal, and 596 laryngeal cancers. Clinical information, including date and type of first treatment, and follow-up were retrieved from the regional Cancer Registry and a population-based health database collecting comprehensive health information on people living in the Region. Multivariate hazard ratio (HR) and confidence intervals (CI) were calculated through Cox model., Results: Overall, the median TTI was 28days, (Q1-Q3: 13-45days), but significant variations emerged according to anatomical site, cancer stage, treatment approach, and care transition to specialized centers. Five-year overall survival decreased with increasing treatment delay from 62% for TTI<30days to 39% for TTI≥90days (p<0.01). HR of death was 1.13 (95% CI: 0.92-1.39) for TTI between 45-89days, and 1.47 (1.05-2.05) for TTI≥90days. The association between TTI and poor prognosis was stronger for laryngeal cancers and early-stage HNSCCs. Further, care transition from community hospitals to specialized centers was associated to a better prognosis (HR=0.73; 95% CI: 0.60-0.88)., Conclusion: Our study findings suggest that HNSCC patients treated within 45days from diagnosis have increased survival probabilities and that early-stage patients suffered the most from treatment delay. Furthermore, care transition to specialized centers -though competitive to timely treatment- improves survival by providing the most innovative technologies and treatment approaches., (Copyright © 2017. Published by Elsevier Ltd.)

Objectives: The World Cancer Research Fund (WCRF) and the American Institute for Cancer Research (AICR) have proposed eight recommendations for cancer prevention, related to body fatness, diet, and physical activity. Our aim is to evaluate the role of adherence to these recommendations on head and neck cancers risk., Materials and Methods: We obtained an overall score including seven of the WCRF/AICR recommendations, and examined its relationship with head and neck cancers risk in two Italian case-control studies including 946 patients with oral cavity and pharyngeal (OCP) cancer and 2492 controls, and 689 patients with laryngeal cancer and 1605 controls., Results: Higher adherence to WCRF/AICR recommendations was associated to a reduced risk of OCP cancer (odds ratio, OR=0.45, 95% confidence interval, CI: 0.33-0.62 for a score of 4-<5, and OR=0.32, 95% CI: 0.22-0.49 for a score of ⩾5 as compared to <3). The ORs for laryngeal cancer were 0.68 (95% CI: 0.50-0.92) for a score of 3-<4, 0.39 (95% CI: 0.28-0.55) for a score of 4-<5, and 0.24 (95% CI: 0.15-0.38) for a score of ⩾5., Conclusion: Our study indicates that high adherence to the WCRF/AICR recommendations for cancer prevention is associated with a substantially decreased risk of head and neck cancers., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction: This study aimed to assess the safety of high doses of radiation delivered with tomotherapy to the intact lung after radical pleurectomy/decortication or biopsy for malignant pleural mesothelioma (MPM)., Methods: Twenty-eight patients were enrolled in this prospective study and underwent adjuvant or definitive tomotherapy after radical pleurectomy/decortication (n = 20) or pleural biopsy (n = 8) for MPM. The dose prescribed to the planning target volume, defined as the entire hemithorax, including chest-wall incisions and drain sites and excluding the intact lung, was 50 Gy delivered in 25 fractions. All patients underwent fluorodeoxyglucose-positron emission tomography for staging after surgery. Any fluorodeoxyglucose-avid areas or regions of particular concern for residual disease were given a simultaneous boost of radiotherapy to 60 Gy. Specific lung dosimetric parameters were reported. Toxicity was graded using the modified Common Toxicity Criteria version 3.0., Results: The median follow-up was of 19 months (range, 6-29 months). Five patients (17.8%) experienced severe respiratory symptoms corresponding to grade 2 pneumonitis in three cases, and grade 3 pneumonitis in two cases. No fatal respiratory toxicity was reported. Controlateral lung V5 was strongly correlated with the risk of pneumonitis. Patients who developed grade 2 and 3 pneumonitis had a higher controlateral lung V5 (mean V5=32%) than those without pneumonitis (mean V5=17%) (p=0.002). Other two grade 3 toxicities were registered: one severe pain to the chest wall, and one severe thrombocytopenia., Conclusions: Tomotherapy allows the safe delivery of high dose of radiation to the hemithorax of MPM patients with intact lung.

To evaluate the outcome of Undifferentiated Nasopharyngeal Carcinomas (UCNT) treated with intensity-modulated radiation therapy with Simultaneous Integrated Boost (SIB), following induction chemotherapy. Between January 2006 and June 2009, 52 patients with stage II B-IVA/B UCNT were treated either with linac-IMRT or Tomotherapy. All patients were scheduled to receive three cycles of cisplatin based neoadjuvant chemotherapy. With a median follow-up of 38.5 months (range 12.3-64.1), 3 year overall survival (OS), disease-free survival (DFS), and DFS by T2a-2b and T3-T4-stage were 95.0%, 84.6%, 89.0%, and 78.0%, respectively. At multivariate analysis, none of the examined prognostic factors reported statistical significance. N-classification was not a significant predictive factor for either OS or development of distant metastases. T-stage alone had a borderline effect on DFS and development of metastases. No difference between Tomotherapy and linac-IMRT emerged in terms of loco-regional control and development of severe, acute, and late toxicities. The most significant severe, acute toxicities were grade 3 (32.7%) and grade 4 (7.7%) mucositis. No grades 3 and 4 late toxicities were observed. The most commonly observed late effect was xerostomia, 11.5% patients complained grade 2 xerostomia. The severity of grade 2 xerostomia diminished over time with only four patients not improving salivation. IMRT-SIB following neoadjuvant chemotherapy was very satisfactory in terms of local control, regional control, DFS and OS rates in patients with stage IIB to IVB UCNT. In our experience, adding concurrent chemotherapy to IMRT after neoadjuvant chemotherapy in loco-regional widespread disease resulted to be the indicated approach., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Nasopharyngeal carcinoma (NPC) is rare in western Countries. Tobacco smoking is a well-recognised risk factor, whereas the role of alcohol drinking is still in debate. We conducted a hospital-based case-control study in Italy on 150, histologically-confirmed, NPC cases of Caucasian ethnicity, aged 18-76years, including 118 undifferentiated NPCs and 22 differentiated squamous-cell NPC. Controls were 450 Caucasian cancer-free patients admitted to general hospitals for acute conditions. Cases and controls were matched according to sex, age, and place of residence. Logistic regression was used to estimate odds ratios (OR) and the corresponding 95% confidence intervals (CI) while adjusting for known confounders. No significant association emerged between tobacco smoking and all NPCs (OR for current vs. never smokers=1.52; 95% CI: 0.89-2.60). Conversely, for differentiated NPC only, statistically significant elevated OR were associated with increasing smoking intensity (OR for ⩾15cigarettes/day=5.40; 95% CI: 1.34-21.76) and duration of the habit (OR for ⩾32years=4.48; 95% CI: 1.11-18.04). Although alcohol drinking was not, per se, significantly associated to NPC risk, the combination of tobacco smoking and alcohol drinking accounted for 57% of differentiated NPCs, whereas it accounted for only 14% of undifferentiated carcinomas. Our findings suggest that, in western populations, NPC includes two separate entities: the differentiated NPC, associated with tobacco smoking like other cancers of head and neck, and the undifferentiated NPC, upon which tobacco smoking has little or no influence., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

High dose pulse intravenous steroids with 1 g of methylprednisolone (MEP) given daily, usually for three days, is an accepted practice to treat severe manifestations of systemic lupus erythematosus (SLE) or systemic vasculitides, despite the lack of definitive data. Most studies addressing the efficacy of high dose glucocorticoids (GCs) have been uncontrolled, retrospective or did not compare different doses. A limited number of studies comparing different doses of GCs suggest that lower doses of MEP given as intravenous pulse therapy might be as effective as the very high doses currently used. In addition, while early reports did not find serious adverse effects related to very high doses of steroids, several more recent studies indicate a high risk of serious infections proportional to the current or cumulative dose of GCs. While we await more conclusive studies addressing these questions, one might wonder whether we could be using too much of a good thing.

The beta-chemokines, MIP-1alpha/CCL3, MIP-1beta/CCL4, and RANTES/CCL5, play a critical role in the selective accumulation and activation of macrophages in inflamed tissues. Herein, we demonstrate that the binding of each of these beta-chemokines to their cognate receptors, CCR1 and CCR5, in either macrophages or in CCR1- or CCR5-transfected CHO cells, induced actin reorganization and the formation of lamellipodia that are characteristic of the activation of the Rho family GTPase, Rac. A dominant negative mutant of Rac, but not dominant negative mutants of RhoA or Cdc42, blocked MIP-1alpha-induced lamellipodia formation. Moreover, this MIP-1alpha-induced Rac activation and consequent lamellipodia formation is Gi- and phosphoinositide-3 kinase (PI3K)-mediated. Thus, Rac activation is critical for both CCR1- and CCR5-triggered signaling cascades mediating beta-chemokine-induced reorganization of the actin cytoskeleton, a process essential for effective recruitment and activation of macrophages in inflammation.

A prospective phase II trial was carried out to evaluate an accelerated chemotherapy (CT) regimen followed by hyperfractionated radiation therapy (RT) in previously untreated Stage III-IV, operable (total laryngectomy), head and neck cancer patients. The current study evaluates overall survival, loco-regional control, organ preservation rates and toxicity. Between April 1997 and December 2002, 68 patients with advanced head and neck cancer were treated with 3 cycles of induction CT (cisplatin and 5-fluorouracil; days 1, 14, and 28) followed by hyperfractionated RT (7440 cGy/62 fractions). Sixty patients received the planned RT-CT treatment. Two months after the end of RT, 96% of patients had a clinical complete remission of the primary and 66% of the neck disease. At a median follow-up of 32 months, the 3-year overall and disease-free survival rates were 66% and 76%, respectively. Seven patients recurred on the primary site, 1 on the neck and 2 patients only had distant metastases. The organ preservation rate was 73%. Acute grade 3-4 mucositis occurred in 75% of patients and an 18% rate of CT-related cardiotoxicity was reported. The accelerated CT-RT regimen achieves a high rate of larynx preservation albeit with considerable toxicity. The current prospective clinical trial was approved by the Ethics Committee of the Centro di Riferimento Oncologico (C.R.O.) on May 27, 1996, # CRO-02-96. Written informed consent was required from all patients entering the study.

Recent data have implicated macrophage inflammatory protein-1alpha (MIP-1alpha) in multiple myeloma (MM)-associated osteolysis. However, it is unclear whether the chemokine's effects are direct, to enhance osteolysis, or indirect and mediated through a reduction in tumor burden, or both. It is also unclear whether MIP-1alpha requires other factors such as receptor activator of nuclear factor-kappaB ligand (RANKL) for its effects on bone. In murine 5TGM1 (Radl) myeloma-bearing mice, administration of neutralizing anti-MIP-1alpha antibodies reduced tumor load assessed by monoclonal paraprotein titers, prevented splenomegaly, limited development of osteolytic lesions, and concomitantly reduced tumor growth in bone. To determine the effects of MIP-1alpha on bone in vivo, Chinese hamster ovary (CHO) cells secreting human MIP-1alpha (CHO/MIP-1alpha) were inoculated into athymic mice. Mice bearing intramuscular CHO/MIP-1alpha tumors developed lytic lesions at distant skeletal sites, which occurred earlier and were larger than those in mice with CHO/empty vector (EV) tumors. When experimental metastases were induced via intracardiac inoculation, mice bearing CHO/MIP-1alpha tumors developed hypercalcemia and significantly more osteolytic lesions than mice bearing CHO/EV tumors, with intramedullary CHO/MIP-1alpha tumors associated with significantly more tartrate-resistant acid phosphatase-positive (TRAP+) osteoclasts. Injection of recombinant MIP-1alpha over calvariae of normal mice evoked a striking increase in osteoclast formation, an effect dependent on RANK/RANKL signaling because MIP-1alpha had no effect in RANK-/- mice. Together, these results establish that MIP-1alpha is sufficient to induce MM-like destructive lesions in bone in vivo. Because, in the 5TGM1 model, blockade of osteoclastic resorption in other situations does not decrease tumor burden, we conclude that MIP-1alpha exerts a dual effect in myeloma, on osteoclasts, and tumor cells.

The aim of this study is to assess the impact of prognostic factors in patients with locoregionally advanced nasopharyngeal cancer (NPC), WHO type II-III, treated with two different radiation therapy (RT) schedules: standard radiation therapy (SRT), and accelerated hyperfractionated radiation therapy (HART), with or without sequential chemotherapy. Between January 1986 and December 1999, 78 consecutive NPC patients were treated either with SRT (until August 1993) or with HART (from September 1993). Of the 78 patients, 60 were males and 18 females, the median age was 56 years (range 14-83). Nine patients had a non-keratinizing carcinoma (WHO type II) and 69 an undifferentiated carcinoma (WHO type III). Five-year overall survival rate (OS) was 62%. Two months after RT, 73 patients were in complete remission. Disease-free survival (DFS) rates at 5 years were: 85% for the HART and 59% for the SRT group, respectively. A multivariate analysis, age (hazard ratio, HR=4.17 for > or = 60 vs. <50 years) and N-stage (HR=3.56 for N3a-N3b vs. N0-N1) were significant for survival, whereas N-stage (HR=8.23 for N3a-N3b vs. N0-N1) and RT schedule (HR=0.30 for HART vs. SRT) were significant for DFS. In our experience, HART achieved higher DFS rates than SRT; however, HART did not favourably affect OS. Toxicity was comparable in the two RT schedules.

We investigated the effect of granulocyte colony-stimulating factor (G-CSF) administration on radiotherapy (RT)-induced oral mucositis in 26 consecutive patients with head and neck neoplasms, stages III and IV, treated with hyperfractionated RT. The first 13 patients were treated with RT alone and the remainder with RT + G-CSF. The two groups of patients were similar in age, sex, PS, primary site, stage, RT schedule and RT volume. Daily mucositis, median mucositis score, day of highest mucositis, requirement of parenteral nutrition, weight loss, treatment break, number of days of RT interruption were analyzed during RT treatment. No statistically significant differences were found between the two groups except for the number of patients who interrupted the treatment: 9/13 patients (69%) in the RT alone group versus 3/13 (23%) in the RT + G-CSF group (p < 0.05). Our observations indicate that G-CSF did not appear to have influenced the objective mucositis although it reduced the number of treatment breaks. In consideration of the cost of G-CSF, its prophylactic administration should be reserved only for patients at high risk of RT interruption.

The aim of this study was to assess the feasibility of concurrent split course radiotherapy and low-dose bleomycin in the treatment of unresectable head and neck cancer with unfavourable prognostic factors and severe symptoms. The clinical outcome of the treatment was assessed in terms of local disease control, symptom relief and toxicity. Between 1990 and 1996, 58 patients with squamous cell carcinoma of the head and neck, stage III or IV, were treated by radiotherapy (50 Gy/20 fractions) and simultaneous bleomycin (60 mg/6 fractions). Local control of disease, overall response, symptom relief and acute toxicity were evaluated. The rate of disease local control was 69% with a median response duration of 7 months (range 2-43+). The symptom relief rate was 81%. Mucositis was the prominent toxicity: G3 mucositis was reported in 27 patients. In conclusion, the treatment was feasible. A good palliation of symptoms and a good rate of local response were obtained. Moreover, toxicity was tolerable and the rate of hospitalisation was low.

We conducted a follow-up study of 380 incident cases of cancer of the oral cavity, pharynx, or larynx, who had been included in a previous case-control study. Information pertaining to potential risk factors, clinical characteristics, and evolution of the tumor (vital status, metastases, and second primary tumors) was obtained. From a multivariate proportional hazard model including terms for risk factors and clinical variables, the incidence of metachronous second primary tumors occurring in the head and neck was positively associated with employment as a farmer as opposed to white collar (hazard ratio [HR] = 3.3) and with tobacco smoking before first tumor diagnosis (HR = 4.3 for heavy versus never or very light smoker). The risk of second primary tumor decreased with increasing dietary "beta-carotene" intake (HR = 0.4 for high versus low intake in tertiles). Less differentiated first primary tumors were followed more frequently by second tumors as compared to grade 1 tumors. The incidence of metastases was not associated with etiological factors of the first tumor, but with stage.