No randomized trials have been conducted to directly compare radiotherapy (RT) with concomitant cisplatin (CDDP) versus concomitant cetuximab (CTX) as first-line treatment of locally advanced ...squamous cell carcinoma of the head and neck. In this randomized trial, we compared these two treatment regimens in terms of compliance, toxicity, and efficacy.
Eligible patients were randomly assigned in a 1:1 ratio to receive either CDDP 40 mg/m(2) once per week or CTX 400 mg/m(2) as loading dose followed by CTX 250 mg/m(2) once per week concomitant to radical RT. For primary end points, compliance to treatment was defined as number of days of treatment discontinuation and drug dosage reduction. The acute toxicity rate was defined according to the National Cancer Institute Common Toxicity Criteria. Efficacy end points were local recurrence-free survival, metastasis-free survival, cancer-specific survival, and overall survival.
The study was discontinued early because of slow accrual after the enrollment of 70 patients. RT discontinuation for more than 10 days occurred in 13% of patients given CTX and 0% given CDDP (P = .05). Drug dosage reduction occurred in 34% given CTX and 53% given CDDP (difference not significant). Toxicity profiles differed between the two arms, with hematologic, renal, and GI toxicities more frequent in the CDDP arm, and cutaneous toxicity and the need for nutritional support more frequent in the CTX arm. Serious adverse events related to treatment, including four versus one toxic deaths, were higher in the CTX arm (19% v 3%, P = .044). Locoregional control, patterns of failure, and survivals were similar between the treatment arms.
CTX concomitant to RT lowered compliance and increased acute toxicity rates. Efficacy outcomes were similar in both arms. These results raise the issue of appropriately selecting patients with head and neck cancer who can benefit from CTX in combination with RT.
Anticancer treatment efficacy is limited by the development of refractory tumor cells characterized by increased expression and activity of mechanisms promoting survival, proliferation, and ...metastatic spread. The present review summarizes the current literature regarding the use of the anthelmintic mebendazole (MBZ) as a repurposed drug in oncology with a focus on cells resistant to approved therapies, including so called "cancer stem cells". Mebendazole meets many of the characteristics desirable for a repurposed drug: good and proven toxicity profile, pharmacokinetics allowing to reach therapeutic concentrations at disease site, ease of administration and low price. Several in vitro studies suggest that MBZ inhibits a wide range of factors involved in tumor progression such as tubulin polymerization, angiogenesis, pro-survival pathways, matrix metalloproteinases, and multi-drug resistance protein transporters. Mebendazole not only exhibits direct cytotoxic activity, but also synergizes with ionizing radiations and different chemotherapeutic agents and stimulates antitumoral immune response. In vivo, MBZ treatment as a single agent or in combination with chemotherapy led to the reduction or complete arrest of tumor growth, marked decrease of metastatic spread, and improvement of survival. Further investigations are warranted to confirm the clinical anti-neoplastic activity of MBZ and its safety in combination with other drugs in a clinical setting.
Cyclin dependent kinases 4/6 (CDK4/6) inhibitors gained an essential role in the treatment of metastatic breast cancer. Nevertheless, data regarding their use in combination with radiotherapy are ...still scarce. We performed a retrospective preliminary analysis of breast cancer patients treated at our Center with palliative radiation therapy and concurrent CDK4/6 inhibitors. Toxicities were measured according to CTCAE 4.0, local response according to RECIST 1.1 or PERCIST 1.0 and pain control using verbal numeric scale. 18 patients (32 treated sites) were identified; 50% received palbociclib, 33.3% ribociclib and 16.7% abemacliclib. Acute non-hematologic toxicity was fair, with the only exception of a patient who developed G3 ileitis. During 3 months following RT, 61.1% of patients developed G 3-4 neutropenia; nevertheless no patient required permanent suspension of treatment. Pain control was complete in 88.2% of patients three months after radiotherapy; 94.4% of patients achieved and maintained local control of disease. Radiotherapy concomitant to CDK4/6 inhibitors is feasible and characterized by a fair toxicity profile, with isolated episodes of high-grade reversible intestinal toxicity. Rate of G 3-4 neutropenia was comparable with that measured for CDK4/6 inhibitors alone. Promising results were reported in terms of pain relief and local control of disease.
Purpose
Fatigue is a distressing symptom in head & neck cancer patients before during and at the end of curative therapy. Pharmacologic and not pharmacologic treatments have been proposed with scarce ...or no evidence of efficacy. The aim of the study is to evaluate the efficacy of American ginseng in respect to placebo in reducing fatigue in patients treated for head and neck cancer with curative intent.
Methods
Thirty-two patients who had completed oncological treatment for a primary Head & neck tumor for at least 1 year and had a global fatigue score > 4 by means of Brief Fatigue Inventory (BFI) were randomized to receive 1000 mg of American ginseng or placebo per day for 8 weeks with the aim to assess their efficacy. Changes in fatigue scores in the 2 subgroups of patients before and after the treatment with American ginseng or placebo, were assessed by the BFI at baseline and at the end of week 8.
Results
The mean of the mean values of the BFI measured at 8 weeks (end of treatment) was 4.6 in the Ginseng arm and 3.4 in the Placebo arm (
p
= ns). Mean comparison showed a tendency to statistical significance only for the single item on interference with general activity (
p
= 0.06), with better performance for placebo. The mean of the differences between baseline values and 8 weeks values was not significantly different between treatment arms considering the entire questionnaire.
Conclusion
The present data shows that American ginseng has insufficient evidence to be recommended for Cancer Related Fatigue (CRF) in post treatment HNC survivors.
This study describes the in vitro and in vivo activity of PXD-101 (Belinostat), a novel hydroxamic acid-type pan-HDACs inhibitor characterized by a larger safety and efficacy, on myogenic-derived ...PAX3/FOXO1 fusion protein positive (RH30) or negative (RD) expressing rhabdomyosarcoma (RMS) cell lines. PXD-101 at low doses efficiently inhibited HDACs activity and counteracted the transformed phenotype of RMS by inducing growth arrest and apoptosis, affecting cancer stem cells population and inducing differentiation in RD. Notably, PXD-101 induced oxidative stress promoting DNA damages and affected the ability of RMS to assemble mitotic spindle. PXD-101 radiosensitized by inducing G2 cell cycle growth arrest, enhancing the radiation's ability to induce ROS accumulation and compromising both the ability of RMS to detoxify from ROS and to repair DNA damage. PXD-101 transcriptionally and post-transcriptionally affected c-Myc expression, key master regulator of rhabdomyosarcomagenesis and RMS radioresistance. All in vitro data were corroborated by in vivo experiments showing the cytostatic effects of PXD-101 when used alone and at low dose and its ability to promote the RT-induced killing of RMS. Taken together, our data confirm that altered HDACs activity plays a key role in RMS genesis and suggest PXD-101 as a valid therapeutic strategy particularly in combination with RT.
•PXD-101 exhibited significant anti-rhabdomyosarcoma activity.•PXD-101 affected stemness, induces differentiation and concomitant cell death.•PXD-101 induced oxidative stress and DNA damage.•PXD-101 interferes with the mitotic spindle assembly.
Objectives
Solitary plasmacytoma (SP) is characterized by a single mass of clonal plasma cells. Definitive RT can result in long-term local control of the SP. Due to the small number of patients and ...narrow range of doses, phase III randomized trials are lacking. The aim of this study is to further support the potential use of RT for the treatment of SP.
Methods
Clinical data of all patients treated for SP at our Institution between 1992 and 2018 were reviewed. A total of 42 consecutive patients were analyzed.
Results
The median follow-up was 84.8 months. Radiation dose did not differ significantly as a function of sex, type of SP (solitary bone plasmacytoma or as extramedullary plasmacytoma), tumor size; conversely differs significantly as a function of age (
p
= 0.04). The 5y-OS and 10y-OS were, respectively, 96 and 91%. Local recurrences developed in 21.4% of patients (9/42). 16 patients progressed to MM (38.1%). The 5y-progression to MM free survival (PMFS) and the 10y-PMFS were, respectively, 68.6 and 61.9%.
Conclusions
Our data confirm that good results are achievable with RT to treat SP, but they don’t allow defining a dose–effect correlation; therefore, it remains uncertain which is the most effective dose and whether lower doses can guarantee adequate disease control.
Objectives
The objective of the paper was to assess real-life experience in the management of head and neck cancer (HNC) patients during the COVID-19 pandemic in radiotherapy departments and to ...evaluate the variability in terms of adherence to American Society of Radiation Oncology (ASTRO) and European Society for Radiotherapy and Oncology (ESTRO) recommendations.
Materials and methods
In May 2020, an anonymous 30-question online survey, comparing acute phase of outbreak and pre-COVID-19 period, was conducted. Two sections exploited changes in general management of HNC patients and different HNC primary tumors, addressing specific statements from ASTRO ESTRO consensus statement as well.
Results
Eighty-eight questionnaires were included in the demographic/clinical workflow analysis, and 64 were analyzed for treatment management. Forty-eight percent of radiotherapy departments became part of oncologic hubs. First consultations reduced, and patients were addressed to other centers in 33.8 and 18.3% of cases, respectively. Telematic consultations were used in 50% of follow-up visits and 73.9% of multidisciplinary tumor board discussions. There were no practical changes in the management of patients affected by different primitive HNCs. Hypofractionation was not favored over conventional schedules.
Conclusions
Compared to pre-COVID era, the clinical workflow was highly re-organized, whereas there were no consistent changes in RT indications and schedules.
We report a subgroup analysis primarily focused on human papillomavirus (HPV)-related oropharyngeal cancer (OPC) from the Cetuximab Plus Radiotherapy Versus Cisplatin Plus Radiotherapy in Locally ...Advanced Head and Neck Cancer (CTXMAB+RT; ClinicalTrials.gov identifier NCT01216020) trial comparing radiation therapy with concomitant cisplatin (CDDP) versus concomitant cetuximab (CTX) as first-line treatment of locally advanced head and neck cancer.
The data from all the patients in the CTXMAB+RT trial were reviewed and separately analyzed in 3 groups: p16-positive OPC, p16-negative OPC, and all other cancer sites. The endpoints of interest were locoregional control (LC), metastasis-free survival, cancer-specific survival (CSS), and overall survival (OS). Severe and fatal infectious complications were also reanalyzed to more thoroughly investigate the association between CTX treatment and potentially life-threatening reactions.
A total of 33 patients had OPC. The HPV status was available for 30 of the 33 patients. Thus, 3 patients treated with CDDP but with unknown HPV status were excluded from the survival analysis. The small number of patients in each group did not allow for significance to be reached for any of the outcomes analyzed. A trend favored the CDDP arm in the p16-positive group for the 2-year LC and OS/CSS rates (100% vs 72.9% and 100% vs 77.8% for CDDP vs CTX). In this group of patients, the hazard ratio for the treatment arm (CTX vs CDDP) was 4.7 (95% confidence interval CI 0.5-40.3) for LC, 3.4 (95% CI 0.4-30.5) for OS, and 2.4 for CSS (95% CI 0.2-23.2). A survival benefit favoring the CDDP arm was not evident in the p16-negative OPC group or for patients with cancer located in other sites. Serious or fatal infectious complications occurred only in the CTX arm.
In patients with p16-positive OPC in the CTXMAB+RT trial, CTX had lower efficacy than CDDP, with possible implications for treatment selection in this clinical setting.
Radio-chemotherapy with CDDP is the standard for H&N squamous cell cancer. CDDP 100 mg/m
/q3 is the standard; alternative schedules are used to reduce toxicity, mostly 40 mg/m
/q1.
Patients were ...treated from 1/2010 to 1/2017 in two Radiation Oncology Centres. Propensity score analysis (PS) was retrospectively used to compare these two schedules.
Patients analyzed were 166. Most (114/166) had 1w-CDDP while 52 had 3w-CDDP. In the 3w-CDDP group, patients were younger, with better performance status, smaller disease extent and a more common nodal involvement than in the 1w-CDDP. Acute toxicity was similar in the groups. Treatment compliance was lower in the w-CCDP. Overall survival before PS was better for female, for oropharyngeal disease and for 3w-CDDP group. After PS, survival was not related to the CDDP schedule.
3w-CDDP remains the standard for fit patients, weekly schedule could be safely used in selected patients.
Purpose
To linguistically validate the Italian translation of the Vanderbilt Head and Neck Symptom Survey (VHNSS), there is a patient-reported outcome measure to screen for symptoms in the head and ...neck cancer (HNC) patients population. The goal was to ensure conceptually equivalence with the original version and maintain clarity, ease of use and understanding.
Methods
We conducted a multi-step linguistic process (forward translation, backward translation and patient testing) to generate and validate an Italian translation of the VHNSS.
Results
Two intermediate Italian versions were created: The first Italian version was derived from a reconciliation of the three forward translations, and the second Italian version was derived from changes in the first version after the backward translation step. All investigators involved actively discussed possible solutions to produce a translated instrument that maintained a reading and comprehension level accessible by most respondents, without altering the meaning and content of the original source. During the patient testing step, only two patients reported problems with items comprehension and the rate of comprehension problems per single item was lower than expected. This phase allowed patients to give suggestion in order to make items clearer and easier to understand: 43% of patients proposed a revision of the survey during the face-to-face interview, and most of these suggestions were retained.
Conclusions
A valid multi-step process leads to the creation of the final version of the VHNSS-IT, a suitable instrument to screen for symptoms in the Italian HNC patients population and an official measurement tool that can be used in cooperative research group.
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