Increase In Late Effects Research Articles

Superficial radiotherapy and volumetric modulated Arc therapy for skin cancers within hamartomatous skin in patient with PTEN mutation: A case report

Phosphatase and tensin homolog (PTEN) gene acts as a tumour suppressor gene. Mutations of this gene are a step in the development of many cancers. Sufferers can have large fields of symptomatic hamartomatous skin change especially in sun exposed areas. RT has been reported to cause increased acute toxicity in this cohort. A 78-year-old fit male had a confirmed PTEN variant LRG_311t1 Exon 5, c353A>C. Symptomatic skin lesions of left frontal scalp and left nasal ala were confirmed on punch biopsy to be basal cell carcinoma (BCC) and he was referred for definitive radiotherapy (RT). He was treated with lesion based superficial radiotherapy to the left nasal ala to a total dose of 50 Gy in 25 fractions given at 5 fractions per week using a Xstrahl 300 machine via a 3cm circle applicator at 30cm source surface distance with a generating energy of 100 kV. The left frontal scalp was treated with a field-based volumetric modulated arc therapy technique to a planning target volume (PTV) of 74.8cm3 to 45 Gy with a simultaneous integrated boost PTV to 55 Gy of 4.1 cm3 to the BCC, all in 25 fractions. He developed the expected desquamation, erythema and mucositis within the nasal field and desquamation and erythema in the left temple. The PTEN mutation had no visible increase on the acute side effect profile compared with those without the mutation. After more than 6 months, the areas treated with RT remained clear of symptomatic hamartomatous skin change with no late toxicities. To our knowledge this is the longest benefit received of any treatment for fields of symptomatic hamartomatous skin change associated with PTEN mutation. It is also a report of not observing increased acute toxicity of RT in the definitive treatment of skin cancer in those with proven PTEN mutation. This one case adds evidence that definitive RT to skin may be delivered safely in this cohort. More studies with multiple patients with longer follow up are needed to confirm that those suffering with PTEN mutation can be safely and successfully treated with definitive RT for skin cancer and fields of symptomatic hamartomatous skin change with no increase in late effects.

Severe late dysphagia and cause of death after concurrent chemoradiation for larynx cancer in patients eligible for RTOG 91-11

The long-term results of RTOG 91-11 suggested increased deaths not attributed to larynx cancer after concomitant chemoradiotherapy (CRT) despite no apparent increase in late effects. Because the timing of events was not reported by RTOG 91-11, one possibility is that severe late dysphagia (SLD) develops beyond five years and leads to unreported treatment-related deaths. Here we explore the timing of SLD after CRT. Patients who would have met eligibility criteria for RTOG 91-11 and were treated with CRT between 1993 and 2013 were identified. Events occurring beyond 3months after treatment and suggestive of SLD were recorded including esophageal stricture dilations, hospital admissions for aspiration pneumonia or feeding-tube insertion. Feeding-tube dependence beyond one year was also considered SLD. The cumulative incidence of SLD and its components was quantified using Gray's competing risk analysis with recurrence or death considered competing risks. Eighty-four patients were included with a median follow-up of 43months. The 5-year overall survival was 70% (95% CI 58-80%). No death was directly a result of treatment-induced late dysphagia. The 5-year incidence of SLD was 26.5%. While 15 of 18 (83%) first stricture dilations occurred within 5years after CRT, 3 of 5 (60%) aspiration admissions and 5 of 8 late feeding tube insertions occurred beyond five years from CRT. SLD is common after CRT for larynx cancer and can occur beyond 5years from the end of treatment, emphasizing the importance of survivorship follow-up. Despite the incidence of SLD, death related to dysphagia is uncommon.

Two-year results from a Swedish study on conventional versus accelerated radiotherapy in head and neck squamous cell carcinoma – The ARTSCAN study

Background and purposeStudies on accelerated fractionation (AF) in head and neck cancer have shown increased local control and survival compared with conventional fractionation (CF), while others have been non-conclusive. In 1998 a national Swedish group decided to perform a randomised controlled clinical study of AF. Materials and methodsPatients with verified squamous cell carcinoma of the oral cavity, oropharynx, larynx (except glottic T1–T2, N0) and hypopharynx were included. Patients with prior chemotherapy or surgery were excluded. Patients were randomised to either CF (2Gy/day, 5days/week for 7 weeks, total dose 68Gy) or to AF (1.1Gy+2.0Gy/day, 5days/week for 4.5weeks, total dose 68Gy). An extensive quality assurance protocol was followed throughout the study. The primary end point was loco-regional tumour control (LRC) at two years after treatment. ResultsThe study was closed in 2006 when 750 patients had been randomised. Eighty-three percent of the patients had stages III–IV disease. Forty eight percent had oropharyngeal, 21% laryngeal, 17% hypopharyngeal and 14% oral cancers. There were no significant differences regarding overall survival (OS) or LRC between the two regimens. The OS at two years was 68% for AF and 67% for CF. The corresponding figures for LRC were 71% and 67%, respectively. There was a trend towards improved LRC for oral cancers treated (p=0.07) and for large tumours (T3–T4) (p=0.07) treated with AF. The AF group had significantly worse acute reactions, while there was no significant increase in late effects. ConclusionOverall the AF regimen did not prove to be more efficacious than CF. However, the trend towards improved results in AF for oral cancers needs to be further investigated.

LONG-TERM CELLULAR EFFECTS IN HUMANS CHRONICALLY EXPOSED TO IONIZING RADIATION

The aim of the study was to investigate hematopoietic injury and recovery in residents of the Techa riverside villages who had been chronically exposed to radiation as a result of the activities of the Mayak Nuclear Facility, and evaluate late effects from chronic, low-dose radiation exposures. Whole blood samples were drawn from 338 unexposed individuals resident in noncontaminated villages, and 692 individuals chronically exposed externally (to primarily gamma radiation) and internally from Sr since 1949 at decreasing dose-rates which have currently reached the background levels. The mean cumulative dose in the exposed cohort was 0.62 Gy over the years 1949 to 2008 using the Techa River Dosimetry System (TRDS) 2000. The frequency of chromosome aberrations and mutations in peripheral lymphocytes, and other aspects indicative of cellular and molecular repair of radiation damage, were measured. The subjects were divided into two study groups: (a) 171 individuals who during the early exposure period (where the highest dose-rates were prevalent) were noted to manifest leucopenia and/or were diagnosed with chronic radiation syndrome (CRS), and (b) 521 exposed individuals without cytopenia and CRS. The first group demonstrated an increased frequency of micronuclei, dicentric chromosomes, somatic mutations (CD3-CD4+cells) in lymphocytes, and mutations in the TP53 gene. In addition, they demonstrated a lower Cu/Zn-SOD concentration, a significantly increased concentration of nitric oxide, and a greater apoptotic frequency in peripheral blood lymphocytes compared to exposed individuals without leucopenia. Similar to the unexposed individuals, the second group demonstrated "background levels" of mutational frequencies several years after their exposures, but they did show an increased number of cells with delayed cell cycles based on Chk-2 concentrations compared to the unexposed population. The data are consistent with the idea that a chronic radiation exposure within a dose range from 0.01 Gy to 1.96 Gy results in more severe late hematopoietic effects in a select cohort of highly radiosensitive individuals, rather than an overall increase in late effects in cells of each exposed individual. The authors state that radiation-exposed subjects demonstrating CRS showed an activation of barrier anti-oxidative stress mechanisms at late periods after radiation exposure, apparently in response to a more severe radiation damage than subjects exposed to similar radiation doses but not demonstrating CRS. Finally, the persistence of chromosome aberrations and somatic mutations in the CRS cohort is indicative of an exhaustion of the anti-oxidative stress mechanisms responding for so many years after the exposure, leading to genomic instability.