The Interplay between Age and Viral Status in EBV-Related Nasopharyngeal and HPV-Related Oropharyngeal Carcinoma Patients.

Background. The aim of this work was to analyze the interplay between age and viral status on the outcomes in loco-regionally advanced oropharyngeal and nasopharyngeal cancer patients treated with radiotherapy and different chemotherapy combinations. Methods. A retrospective (2006−2017) analysis was performed on non-metastatic loco-regionally advanced oropharyngeal (both HPV+ and HPV−) and EBV+ nasopharyngeal cancer patients (young: <65 years vs. elderly: ≥65 years) treated with radiotherapy with or without chemotherapy. The impact of age and viral status on overall (OS) and disease-free survival (DFS) were studied with multivariable models, which were adjusted for smoking, stage, comorbidities, chemotherapy dose intensity and treatment strategy. Results. We analyzed 324 patients (146 HPV+ oropharynx, 63 HPV−, 115 nasopharynx). Elderly patients had more comorbidities, and received less intensive treatments when compared to younger subjects. Although OS and DFS were shorter in older patients, after adjustment for stage, smoking, comorbidities, treatment strategy and dose intensity, no significant differences in terms of survival were observed according to age (65 vs. 50 years of age: HR 1.89, 95% CI 0.45−7.84 for HPV+ OPC; HR 0.91, 95% CI 0.29−2.89 for HPV− OPC; HR 1.99, 95% CI 0.9−4.39 for NPC; p = 0.395). Conclusions. Several potential age-related (comorbidities, treatment intensity) and disease-related (stage) confounding factors play a prognostic role with differential impacts on both virus and non-virus-related tumors. In HPV+ oropharyngeal cancer and in EBV+ nasopharyngeal cancer patients, age should be considered as the expression of an array of host- and tumor-related features rather than an independent prognostic factor.

Management of loco-regionally advanced squamous laryngeal cancer in elderly patients.

PURPOSE: To describe the management and outcomes of loco-regionally advanced (stages III-IV) laryngeal cancer (LRALC) in elderly patients. METHODS: Clinical records of 88 LRALC patients treated at our Institution from 2002 to 2017 were retrospectively reviewed. Patients were divided in 2 subgroups: age > 65 years (elderly) and age ≤ 65 years (controls). Survivals were estimated with Kaplan-Meier method and compared with log-rank test, multivariate analysis were performed with Cox proportional hazard methods. RESULTS: Eighty-eight LRALC patients were included: 45 elderly and 43 controls. Median follow-up was 55.3 months. Median age was 66 years (range 41-84) in the overall population, 72 years (range 66-84) in the elderly cohort. The majority (98%) of elderly patients had at least one comorbidity (ACE27 1-3), while ACE27 was 0 in 37% of controls (p = 0.0001). ECOG PS was 0 in 42% of elderly vs 79% of controls (p = 0.0029). Clinical stage (TNM eighth edition) was III in 67%, IVA in 22% and IVB in 11%. Treatment consisted in total laryngectomy (TL) in 55%, chemo-radiation in 29%, exclusive radiotherapy in 9%, and conservative surgery in 7%. In elderly patients 2-year disease-free and overall survivals were 58% and 74%, respectively. Multivariate analysis performed on the overall group of 88 patients showed that age (HR 1.07, p = 0.0006) and TNM (for both 7th and 8th Editions HR 0.27 for stage III vs IV, p = 0.0005) maintained an independent statistical significant association with OS. CONCLUSIONS: In this monocentric cohort, age and TNM confirmed their independent prognostic role in LRALC patients. Organ-preservation is still an unmet need in a significant portion of elderly patients.

Role of IMRT/VMAT-Based Dose and Volume Parameters in Predicting 5-Year Local Control and Survival in Nasopharyngeal Cancer Patients.

Objective: This study aimed to look into the relationship between intensity-modulated-radiotherapy (IMRT)- or volumetric-modulated-arc-therapy (VMAT)-based dose-volume parameters and 5-year outcome for a consecutive series of non-metastatic nasopharyngeal cancer (NPC) patients (pts) treated in a single institution in a non-endemic area in order to identify potential prognostic factors. Materials and methods: A retrospective analysis of consecutive non-metastatic NPC pts treated curatively with IMRT or VMAT and chemotherapy (CHT) between 2004 and 2014 was conducted. One patient was in stage I (0.7%), and 24 pts (17.5%) were in stage II, 38 pts (27.7%) in stage III, 29 pts (21.2%) in stage IVA, and 45 pts (32.8%) in stage IVB. Five pts (3.6%) received radiotherapy (RT) alone. Of the remaining 132 pts (96.4%), 30 pts (21.9%) received CHT concomitant to RT, and 102 pts (74.4%) were treated with induction CHT followed by RT-CHT. IMRT was given with standard fractionation at a total dose of 70 Gy. Clinical outcomes investigated in the study were local control (LC), disease-free survival (DFS), and overall survival (OS). Kaplan-Meier (KM) analysis was performed for the outcomes considering dose and coverage parameters, staging, and RT technique. Results: Overall, 137 pts were eligible for this retrospective analysis. With a median follow-up of 70 months (range 12-143), actuarial rates at 5 years were LC 90.4, DFS 77.2, and OS 82.8%. For this preliminary study, T stage was dichotomized as T1, T2, T3 vs. T4. At 5 years, the group T1-T2-T3 reported an LC of 93%, a DFS of 79%, and an OS of 88%, whereas T4 pts reported LC, DFS, and OS, respectively, of 56, 50, and 78%. Pts with V95% > 95.5% had better LC (p = 0.006). Pts with D99% > 63.8 Gy had better LC (p = 0.034) and OS (p = 0.005). The threshold value of 43.2 cm3 of GTVT was prognostic for LC (p = 0.016). To predict the risk of local recurrence at 5 years, we constructed a nomogram which combined GTVT with D99% relative to HRPTV. Conclusions: We demonstrated the prognostic value of some dose-volume parameters, although in a retrospective series, this is potentially useful to improve planning procedure. In addition, for the first time in a non-endemic area, a threshold value of GTVT, prognostic for LC, has been confirmed.

A monocentric, open-label randomized standard-of-care controlled study of XONRID®, a medical device for the prevention and treatment of radiation-induced dermatitis in breast and head and neck cancer patients.

BACKGROUND: This study was an open-label, 2-arms, monocentric, randomized clinical trial comparing Xonrid®, a topical medical device, versus standard of care (SOC) in preventing and treating acute radiation dermatitis (ARD) in Head and Neck Cancer (HNC) and Breast Cancer (BC) patients undergoing radiotherapy (RT). METHODS: Eligible HNC and BC patients were randomized 1:1 to receive Xonrid® + SOC or SOC during RT. Patients were instructed to apply Xonrid® on the irradiated area three times daily, starting on the first day of RT and until 2 weeks after RT completion or until the development of grade ≥ 3 skin toxicity. The primary endpoint was to evaluate the proportion of patients who developed an ARD grade < 2 at the 5th week in both groups. Secondary endpoints were median time to grade 2 (G2) skin toxicity onset; changes in skin erythema and pigmentation and trans-epidermal water loss (TEWL); patient-reported skin symptoms. All patients were evaluated at baseline, weekly during RT and 2 weeks after treatment completion. The evaluation included: clinical toxicity assessment; reflectance spectrometry (RS) and TEWL examination; measurement of patients' quality of life (QoL) through Skindex-16 questionnaire. RESULTS: Eighty patients (40 for each cancer site) were enrolled between June 2017 and July 2018. Groups were well balanced for population characteristics. All BC patients underwent 3-Dimensional Conformal RT (3D-CRT) whereas HNC patients underwent Volumetric-Modulated Arc Therapy (VMAT). At week 5 the proportion of BC patients who did not exhibit G2 ARD was higher in Xonrid® + SOC group (p = 0.091). In the same group the onset time of G2 ARD was significantly longer than in SOC-alone group (p < 0.0491). For HNC groups there was a similar trend, but it did not reach statistical significance. For both cancer sites, patients' QoL, measured by the Skindex-16 score, was always lower in the Xonrid® + SOC group. CONCLUSION: Despite the failure to achieve the primary endpoint, this study suggests that Xonrid® may represent a valid medical device in the prevention and treatment of ARD at least in BC patients, delaying time to develop skin toxicity and reducing the proportion of patients who experienced G2 ARD during RT treatment and 2 weeks later. TRIAL REGISTRATION: The study was approved by the Ethical Committee of Fondazione IRCCS Istituto Nazionale dei Tumori di Milano (INT 52/14 - NCT02261181 ). Registered on ClinicalTrial.gov on 21st August 2017.

Postoperative radiotherapy (PORT) for early oral cavity cancer (pT1-2,N0-1): A review.

Early stage (T1-2, N0-1) oral squamous cell carcinoma (OSCC) has a generally favorable prognostic outcome. However, locoregional recurrences can occur in up to 30-35% of patients, and 20% will eventually die of disease. National and international treatment guidelines do not recommend the use of postoperative radiotherapy (PORT) in a setting of early OSCC, and highlight surgery alone as the standard single modality treatment. Notwithstanding, the negative prognostic impact of some adverse pathological features, such as perineural and lymphovascular invasion, poor differentiation, depth of invasion >4 mm, and presence of nodal metastasis, is well known. The advantages of PORT in such scenarios are still debated. The aim of this study was to review the more recent literature to provide evidence on the benefits of PORT in the context of early stage OSCC.