Stereotactic Body Radiotherapy for Large Unresectable Hepatocellular Carcinomas - A Single Institution Phase II Study.

AIMS: To evaluate the safety and efficacy of liver stereotactic body radiotherapy (SBRT) in the treatment of unresectable hepatocellular carcinomas (HCC) measuring >5 cm. MATERIALS AND METHODS: Between November 2013 and February 2016, 13 patients with unresectable HCC (>5 cm), ineligible for other local treatments, with a Child-Pugh score (CPS) ≤ B7, were enrolled into a single-institution phase II study. SBRT was delivered by volumetric-modulated arc radiotherapy. Radiological response was reported using modified Response Evaluation Criteria in Solid Tumours criteria and toxicities graded by Common Terminology Criteria for Adverse Events v4 criteria. RESULTS: Sixteen hepatomas (median size 7.5 cm, range 5.1-9.7 cm) were treated in 13 patients. The baseline CPS was A5/6 in nine patients (69%) and B7 in four patients (31%). Five patients (38%) received previous liver-directed treatment. The median prescribed dose was 45 Gy (range 40-45 Gy) in five fractions. The median follow-up was 17.7 months. The 1-year local control rate was 92%. The median overall survival was 17.7 months and the 1-year overall survival was 62%. The median time to local progression was not reached. Five patients (39%) had an increase in CPS by two or more points at 3 months. Overall, there were 10 grade 3 acute toxicities occurring in seven patients, of which six were haematological. Quality of life remained clinically stable or improved at 3 months in 61.5% and 53.8% of patients based on the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 Global Health Score and Functional Assessment of Cancer Therapy - Hepatobiliary version 4 score, respectively. CONCLUSIONS: In our cohort, SBRT to unresectable large HCC tumours provided excellent local control with acceptable toxicities. Regional recurrence remained the major cause of failure. Further studies are warranted to examine the role for SBRT in combination with other modalities to maximise disease control in the liver.

"Another thing to live for": Supporting HCV treatment and cure among Indigenous people impacted by substance use in Canadian cities.

BACKGROUND: Colonization and colonial systems have led to the overrepresentation of Indigenous people impacted by substance use and HCV infection in Canada. It is critical to ensure Indigenous people's equitable access to new direct acting antiviral HCV treatments (DAAs). Identifying culturally-safe, healing-centered approaches that support the wellbeing of Indigenous people living with HCV is an essential step toward this goal. We listened to the stories and perspectives of HCV-affected Indigenous people and HCV treatment providers with the aim of providing pragmatic recommendations for decolonizing HCV care. METHODS: Forty-five semi-structured interviews were carried out with Indigenous participants affected by HCV from the Cedar Project (n = 20, British Columbia (BC)) and the Canadian Coinfection Cohort (n = 25, BC; Ontario (ON); Saskatchewan (SK)). In addition, 10 HCV treatment providers were interviewed (n = 4 BC, n = 4 ON, n = 2 SK). Interpretive description identified themes to inform clinical approaches and public health HCV care. Themes and related recommendations were validated by Indigenous health experts and Indigenous participants prior to coding and re-contextualization. RESULTS: Taken together, participants' stories and perceptions were interpreted to coalesce into three overarching and interdependent themes representing their recommendations. First: treatment providers must understand and accept colonization as a determinant of health and wellness among HCV-affected Indigenous people, including ongoing cycles of child apprehension and discrimination within the healthcare system. Second: consistently safe attitudes and actions create trust within HCV treatment provider-patient relationships and open opportunities for engagement into care. Third: treatment providers who identify, build, and strengthen circles of care will have greater success engaging HCV-affected Indigenous people who have used drugs into care. CONCLUSION: There are several pragmatic ways to integrate Truth and Reconciliation as well as Indigenous concepts of whole-person wellness into the HCV cascade of care. By doing so, HCV treatment providers have an opportunity to create greater equity and support long-term wellness of Indigenous patients.

Dose reconstruction from PET images in carbon ion therapy: a deconvolution approach.

Dose and range verification have become important tools to bring carbon ion therapy to a higher level of confidence in clinical applications. Positron emission tomography is among the most commonly used approaches for this purpose and relies on the creation of positron emitting nuclei in nuclear interactions of the primary ions with tissue. Predictions of these positron emitter distributions are usually obtained from time-consuming Monte Carlo simulations or measurements from previous treatment fractions, and their comparison to the current, measured image allows for treatment verification. Still, a direct comparison of planned and delivered dose would be highly desirable, since the dose is the quantity of interest in radiation therapy and its confirmation improves quality assurance in carbon ion therapy. In this work, we present a deconvolution approach to predict dose distributions from PET images in carbon ion therapy. Under the assumption that the one-dimensional PET distribution is described by a convolution of the depth dose distribution and a filter kernel, an evolutionary algorithm is introduced to perform the reverse step and predict the depth dose distribution from a measured PET distribution. Filter kernels are obtained from either a library or are created for any given situation on-the-fly, using predictions of the [Formula: see text]-decay and depth dose distributions, and the very same evolutionary algorithm. The applicability of this approach is demonstrated for monoenergetic and polyenergetic carbon ion irradiation of homogeneous and heterogeneous solid phantoms as well as a patient computed tomography image, using Monte Carlo simulated distributions and measured in-beam PET data. Carbon ion ranges are predicted within less than 0.5 mm and 1 mm deviation for simulated and measured distributions, respectively.

Experimental validation of the FLUKA Monte Carlo code for dose and [Formula: see text]-emitter predictions of radioactive ion beams.

In the context of hadrontherapy, whilst ions are capable of effectively destroying radio resistant, deep seated tumors, their treatment localization must be well assessed to ensure the sparing of surrounding healthy tissue and treatment effectiveness. Thus, range verification techniques, such as online positron-emission-tomography (PET) imaging, hold great potential in clinical practice, providing information on the in vivo beam range and consequent tumor targeting. Furthermore, [Formula: see text] emitting radioactive ions can be an asset in online PET imaging, depending on their half-life, compared to their stable counterparts. It is expected that using these radioactive ions the signal obtained by a PET apparatus during beam delivery will be greatly increased, and exhibit a better correlation to the Bragg Peak. To this end, FLUKA Monte Carlo particle transport and interaction code was used to evaluate, in terms of annihilation events at rest and dose, the figure of merit in using [Formula: see text] emitter, radioactive ion beams (RI [Formula: see text]). For this purpose, the simulation results were compared with experimental data obtained with an openPET prototype in various online PET acquisitions at the Heavy Ion Medical Accelerator in Chiba (HIMAC), in collaboration with colleagues from the National Institute of Radiological Sciences' (NIRS) Imaging Physics Team. The dosimetry performance evaluation with FLUKA benefits from its recent developments in fragmentation production models. The present work estimated that irradiations with RI [Formula: see text], produced via projectile fragmentation and their signal acquisition with state-of-the-art PET scanner, lead to nearly a factor of two more accurate definition of the signals' peak position. In addition to its more advantageous distribution shape, it was observed at least an order magnitude higher signal acquired from 11C and 15O irradiations, with respect to their stable counterparts.

Shift in disparities in hepatitis C treatment from interferon to DAA era: A population-based cohort study.

We evaluated the shift in the characteristics of people who received interferon-based hepatitis C virus (HCV) treatments and those who received recently introduced direct-acting antivirals (DAAs) in British Columbia (BC), Canada. The BC Hepatitis Testers Cohort includes 1.5 million individuals tested for HCV or HIV, or reported cases of hepatitis B and active tuberculosis in BC from 1990 to 2013 linked to medical visits, hospitalization, cancer, prescription drugs and mortality data. This analysis included all patients who filled at least one prescription for HCV treatment until 31 July 2015. HCV treatments were classified as older interferon-based treatments including pegylated interferon/ribavirin (PegIFN/RBV) with/without boceprevir or telaprevir, DAAs with RBV or PegIFN/RBV, and newer interferon-free DAAs. Of 11 886 people treated for HCV between 2000 and 2015, 1164 (9.8%) received interferon-free DAAs (ledipasvir/sofosbuvir: n=1075; 92.4%), while 452 (3.8%) received a combination of DAAs and RBV or PegIFN/RBV. Compared to those receiving interferon-based treatment, people with HIV co-infection (adjusted odds ratio [aOR]: 2.96, 95% CI: 2.31-3.81), cirrhosis (aOR: 1.77, 95% CI: 1.45-2.15), decompensated cirrhosis (aOR: 1.72, 95% CI: 1.31-2.28), diabetes (aOR: 1.30, 95% CI: 1.10-1.54), a history of injection drug use (aOR: 1.34, 95% CI: 1.09-1.65) and opioid substitution therapy (aOR: 1.30, 95% CI: 1.01-1.67) were more likely to receive interferon-free DAAs. Socio-economically marginalized individuals were significantly less likely (most deprived vs most privileged: aOR: 0.71, 95% CI: 0.58-0.87) to receive DAAs. In conclusion, there is a shift in prescription of new HCV treatments to previously excluded groups (eg HIV-co-infected), although gaps remain for the socio-economically marginalized populations.

Trends in health care utilization and costs attributable to hepatocellular carcinoma, 2002-2009: a population-based cohort study.

BACKGROUND: The incidence of hepatocellular carcinoma (hcc) and the complexity of its diagnosis and treatment are increasing. We estimated trends in net health care utilization, costs of care attributable to hcc in Ontario, and rate ratios of resource use at various stages of care. METHODS: This population-based retrospective cohort study identified hcc patients and non-cancer control subjects, and health care resource utilization between 2002 and 2009. Generalized estimating equations were then used to estimate net health care utilization (hcc patients vs. the matched control subjects) and net costs of care attributable to hcc. Generalized linear models were used to analyze rate ratios of resource use. RESULTS: We identified 2832 hcc patients and 2808 matched control subjects. In comparison with the control subjects, hcc patients generally used a greater number of health care services. Overall, the mean net cost of care per 30 patient-days (2013 Canadian dollars) attributable to outpatient visits and hospitalizations was highest in the pre-diagnosis (1 year before diagnosis), initial (1st year after diagnosis), and end-of-life (last 6 months before death, short-term survivors) phases. Mean net homecare costs were highest in the end-of-life phase (long-term survivors). In the end-of-life phase (short-term survivors), mean net costs attributable to outpatient visits and total services significantly increased to $14,220 from $1,547 and to $33,121 from $14,450 (2008-2009 and 2002-2003 respectively). CONCLUSIONS: In hcc, our study found increasing resource use and net costs of care, particularly in the end-of-life phase among short-term survivors. Our findings offer a basis for resource allocation decisions in the area of cancer prevention and control.

Open-label study of faldaprevir plus peginterferon and ribavirin in hepatitis C virus genotype 1-infected patients who failed placebo plus peginterferon and ribavirin.

Faldaprevir, a hepatitis C virus (HCV) NS3/4A protease inhibitor, was evaluated in HCV genotype 1-infected patients who failed peginterferon and ribavirin (PegIFN/RBV) treatment during one of three prior faldaprevir trials. Patients who received placebo plus PegIFN/RBV and had virological failure during a prior trial were enrolled and treated in two cohorts: prior relapsers (n = 43) and prior nonresponders (null responders, partial responders and patients with breakthrough; n = 75). Both cohorts received faldaprevir 240 mg once daily plus PegIFN/RBV for 24 weeks. Prior relapsers with early treatment success (ETS; HCV RNA <25 IU/mL detectable or undetectable at week 4 and <25 IU/mL undetectable at week 8) stopped treatment at week 24. Others received PegIFN/RBV through week 48. The primary efficacy endpoint was sustained virological response (HCV RNA <25 IU/mL undetectable) 12 weeks post treatment (SVR12). More prior nonresponders than prior relapsers had baseline HCV RNA ≥ 800,000 IU/mL (80% vs 58%) and a non-CC IL28B genotype (91% vs 70%). Rates of SVR12 (95% CI) were 95.3% (89.1, 100.0) among prior relapsers and 54.7% (43.4, 65.9) among prior nonresponders; corresponding ETS rates were 97.7% and 65.3%. Adverse events led to faldaprevir discontinuations in 3% of patients. The most common Division of AIDS Grade ≥ 2 adverse events were anaemia (13%), nausea (10%) and hyperbilirubinaemia (9%). In conclusion, faldaprevir plus PegIFN/RBV achieved clinically meaningful SVR12 rates in patients who failed PegIFN/RBV in a prior trial, with response rates higher among prior relapsers than among prior nonresponders. The adverse event profile was consistent with the known safety profile of faldaprevir.

Influence of intra-oral sensory impairment by anaesthesia on food comminution and mixing in dentate subjects.

Sensory input from sensory receptors regarding food morsels can affect jaw motor behaviours during mastication. The aim was to clarify the effects of intra-oral sensory input on the food-comminuting and food-mixing capacities of dentate subjects. Eleven dentate subjects without sensory dysfunction in their oro-facial region participated in this study. Local anaesthesia was achieved on the periodontal structures and on the oral mucosa of the subjects' preferred chewing side by injecting a lidocaine solution with adrenalin. At baseline (control) and after anaesthesia, data on the subjects' food-comminuting and food-mixing capacities were gathered. The food-comminuting capacity was quantified by measuring the degree of pulverisation of peanuts (objective hardness; 45.3 [Newton, N]) after a prescribed 20 chewing strokes. The food-mixing capacity was measured as the degree of immixture of a two-coloured paraffin wax cube after 10 chewing strokes. Wax cubes of three different hardness levels were used (soft, medium and hard: 20.3, 32.6 and 75.5 [N], respectively) and were chewed in random order. After anaesthesia, the subjects' food-comminuting capacity significantly decreased (P < 0.001), as did the food-mixing capacity for each hardness level of the wax cubes (P < 0.01). A significant correlation was observed between the objective hardness values and the anaesthesia effects for the food-mixing capacity (P < 0.05), indicating that after anaesthesia, deterioration of the mixing capacity increased as the hardness increased. In conclusion, intra-oral sensory input can affect both food-comminuting and food-mixing capacities.

Solid organ transplant recipients: clinical considerations in the application of exercise.

Over 100 000 solid organ transplants are performed worldwide each year and this has a significant impact on physical function and quality of life. However, the capacity for exercise in solid-organ recipients is reduced. Regular physical activity improves most of the indices of fitness in these patients but, with few exceptions, they do not reach the values seen in healthy controls. The reason for the 40-60% reduction in maximal exercise capacity is not clear; the disease process, need for life long immunosuppression and sedentary lifestyle all contribute. The interaction between exercise and immunosuppressing medication merits research as does the specifics of the exercise prescription for these patients. This paper reviews important features of this rapidly expanding group of patients and suggests clinical considerations in the application of exercise in this population.

Compact 100Gb/s DP-QPSK integrated receiver module employing three-dimensional assembly technology.

We demonstrate a compact 100 Gbit/s DP-QPSK receiver module that is only 18 mm (W) x 16 mm (D) x 2.8 mm (H). The module size is reduced by using a ball grid array (BGA) package with three-dimensional assembly technology and by applying a heterogeneous integrated PLC. Error-free DP-QPSK signal demodulation is successfully demonstrated.

Two-colour chewing gum mixing ability: digitalisation and spatial heterogeneity analysis.

Many techniques are available to assess masticatory performance, but not all are appropriate for every population. A proxy suitable for elderly persons suffering from dementia was lacking, and a two-colour chewing gum mixing ability test was investigated for this purpose. A fully automated digital analysis algorithm was applied to a mixing ability test using two-coloured gum samples in a stepwise increased number of chewing cycles protocol (Experiment 1: n = 14; seven men, 19-63 years), a test-retest assessment (Experiment 2: n = 10; four men, 20-49 years) and compared to an established wax cubes mixing ability test (Experiment 3: n = 13; 0 men, 21-31 years). Data were analysed with repeated measures anova (Experiment 1), the calculation of the intraclass correlation coefficient (ICC; Experiment 2) and Spearman's rho correlation coefficient (Experiment 3). The method was sensitive to increasing numbers of chewing cycles (F5,65 = 57·270, P = 0·000) and reliable in the test-retest (ICC value of 0·714, P = 0·004). There was no significant correlation between the two-coloured gum test and the wax cubes test. The two-coloured gum mixing ability test was able to adequately assess masticatory function and is recommended for use in a population of elderly persons with dementia.

Adherence to assigned dosing regimen and sustained virological response among chronic hepatitis C genotype 1 patients treated with boceprevir plus peginterferon alfa-2b/ribavirin.

BACKGROUND: Adherence to therapeutic regimens affects the efficacy of peginterferon alfa (P) and ribavirin (R) therapy in patients with chronic hepatitis C virus genotype 1. AIM: To determine if medication adherence impacts efficacy [sustained virological response (SVR)] with triple therapy that includes boceprevir (BOC) plus P/R. METHODS: Adherence was determined in two Phase 3 clinical studies with BOC: SPRINT-2 (previously untreated patients) and RESPOND-2 (patients who failed previous therapy with P/R). Adherence to the assigned duration of the dosing regimen and adherence to the three times a day (t.d.s.) dosing interval of 7-9 h for BOC were assessed by the recording of data from patients' dosing diaries and by the amount of study drug dispensed and returned. RESULTS: Most patients (63-71%) adhered to ≥80% of their assigned treatment duration and achieved SVR rates of 86-90%. In contrast, patients who adhered to <80% of their assigned treatment duration achieved SVR rates of 8-32% (P < 0.0001), particularly low in patients who failed previous therapy (SVR = 8-15%). Different rates of adherence (<60% to >80%) to the t.d.s. dosing interval (7-9 h) with BOC did not influence the SVR rates (SVR = 60-83%) with the exception of patients who failed previous treatment and adhered to <60% of the t.d.s. dosing interval with BOC (SVR = 48-50%; P = 0.005). CONCLUSIONS: The achievement of an SVR is more dependent on adherence to the assigned duration of treatment than adherence to the t.d.s. dosing interval with boceprevir. Adherence to >60% of t.d.s. dosing with boceprevir is important in patients who failed previous therapy.

Barriers to transplantation in adults with inborn errors of metabolism.

BACKGROUND: Transplantation in patients with inborn errors of metabolism (IEM) may be used as rescue therapy for acute decompensation, organ replacement, or disease-modifying therapy. We sought to quantify the use of transplantation in adults with IEM. METHODS: A 10-question online survey was sent through the email list of adult IEM physicians maintained by the Society for the Study of Inborn Errors of Metabolism and posted on the website of the Society of Inherited Metabolic Diseases. RESULTS: Thirteen centers from five continents responded. These centers, ranging in size from <50 adult patients (three centers) to >500 (two centers), reported 57 adult patients who had undergone transplantation. 29/57 (51 %) came from the two largest centers and 27/57(47 %) were renal transplants for Fabry disease (FD). Only seven transplants were identified as being done for acute decompensation. Eight of thirteen centers had not had patients with IEM passed over on the transplant list but four of these eight had not referred a patient for transplantation. 4/13 centers had patients passed over on the transplant list and reasons cited included: (a) transplant team not comfortable with underlying disease, (b) cognitive impairment in patient raised concerns about compliance, (c) multisystem disease makes single organ transplantation inappropriate, and (d) not at enough risk of life-threatening decompensation. CONCLUSIONS: Excluding renal transplantation for FD, there is low use of transplantation in adults with IEM. Some barriers to transplantation reported by adult centers could be improved with development of educational and management modules for both transplant and metabolic programs.

Association between occlusal curvature and food comminution and mixing in human young adults with permanent dentitions.

OBJECTIVE: Occlusal curvatures in human adult dentition such as the curve of Spee, curve of Wilson and Monsons's sphere provide clinical guidance for prosthetic rehabilitation and orthodontic treatment. However, association between occlusal curvature and masticatory function is not known. The aim of this study was to investigate the association between occlusal curvature and food comminuting and food mixing ability in human young adults with permanent dentitions. DESIGN: Fifty young adults with complete dentitions (mean age, 25.0 years) participated in the study. Occlusal curvature was determined by a three-dimensional analysis of the mandibular arch according to the Broadrick flag method. Food comminuting ability was assessed using a masticatory performance test with peanuts as test food and it was scored as median particle size. Food mixing ability was assessed using a mixing ability test with a two-coloured wax cube and it was scored as mixing ability index. RESULTS: A linear regression analysis identified the sphere radius of occlusal curvature as significant predictor for both median particle size and mixing ability index after controlling for maximum bite force (P<0.001). These results indicated that subjects with a flatter curvature (larger sphere) in the mandibular arch showed better food comminuting and mixing ability. Coefficient of determination (R(2)) of occlusal curvature related to median particle size and mixing ability index was comparable to that of maximum bite force. CONCLUSION: Occlusal curvature seems to be associated with food comminuting and mixing ability in human young adults with permanent dentitions.

Hepatic embolotherapy in interventional oncology: technology, techniques, and applications.

Embolotherapy continues to play a growing role in the management of primary and secondary hepatic malignancies. In this review article, we examine the basis of therapy with a focus on neovascularization, which makes treatments via the hepatic artery possible. An overview of the three generations of embolic and therapeutic agents follows. The techniques, technologies, and complications of bland embolization, transarterial chemoembolization, drug-eluting beads, and selective internal radiotherapy are covered to give the reader an overview of this exciting field in interventional radiology.

Meta-analysis of genome-wide association studies for panic disorder in the Japanese population.

Panic disorder (PD) is a moderately heritable anxiety disorder whose pathogenesis is not well understood. Due to the lack of power in previous association studies, genes that are truly associated with PD might not be detected. In this study, we conducted a genome-wide association study (GWAS) in two independent data sets using the Affymetrix Mapping 500K Array or Genome-Wide Human SNP Array 6.0. We obtained imputed genotypes for each GWAS and performed a meta-analysis of two GWAS data sets (718 cases and 1717 controls). For follow-up, 12 single-nucleotide polymorphisms (SNPs) were tested in 329 cases and 861 controls. Gene ontology enrichment and candidate gene analyses were conducted using the GWAS or meta-analysis results. We also applied the polygenic score analysis to our two GWAS samples to test the hypothesis of polygenic components contributing to PD. Although genome-wide significant SNPs were not detected in either of the GWAS nor the meta-analysis, suggestive associations were observed in several loci such as BDKRB2 (P=1.3 × 10(-5), odds ratio=1.31). Among previous candidate genes, supportive evidence for association of NPY5R with PD was obtained (gene-wise corrected P=6.4 × 10(-4)). Polygenic scores calculated from weakly associated SNPs (P<0.3 and 0.4) in the discovery sample were significantly associated with PD status in the target sample in both directions (sample I to sample II and vice versa) (P<0.05). Our findings suggest that large sets of common variants of small effects collectively account for risk of PD.

Pneumocystis pneumonia in solid organ transplant recipients: not yet an infection of the past.

BACKGROUND: Solid organ transplant (SOT) recipients are at risk for Pneumocystis pneumonia (PCP), especially in the first year post transplant. Although trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis substantially decreases this risk, there is little data or consensus on optimal duration of prophylaxis. Consequently, there is lack of standardization of prophylaxis duration (3 months to lifelong, depending on organ group) in SOT programs. METHODS: We performed a retrospective chart review of all cases of confirmed PCP, in adult kidney, pancreas, liver, and lung transplant recipients from 2001 to 2011 in our SOT program. RESULTS: Of 1241 patients followed in our clinic (657 kidney, 44 kidney/pancreas, 436 liver, and 104 lung or heart/lung), a total of 14 PCP cases were identified in 2 kidney, 1 kidney/pancreas, 5 liver, 5 single lung, and 1 heart/lung transplant recipient. At the time of PCP diagnosis, immunosuppression in most cases consisted of prednisone, tacrolimus, and mycophenolate mofetil (79% of patients), and 53% had previously received TMP-SMX for prophylaxis. None were on PCP prophylaxis at the time of illness onset. PCP occurred early in all 5 liver transplant recipients and in 1 kidney transplant recipient, none of whom had ever received prophylaxis (17-204 days post transplant). Of those who had received 6 months of prophylaxis (1 kidney, 1 kidney/pancreas), PCP occurred at 846 and 4778 days, respectively. Late onset PCP occurred in lung recipients who had received 12 months of prophylaxis (lung 645-1414 days, heart/lung 1583 days post transplant). Five patients had experienced acute rejection and 6 patients had cytomegalovirus (CMV) viremia on average 59 and 204 days preceding PCP, respectively. Three deaths (1 liver, 2 lung) were thought to be directly related to complications of PCP. CONCLUSION: Our experience with late PCP cases in lung transplant recipients receiving only 1 year of prophylaxis lends support to prolonged PCP prophylaxis in this group. Given the number of patients who had experienced an acute rejection episode or CMV disease preceding PCP in non-lung SOT recipients, consideration should be given to re-institution of PCP prophylaxis for a period of time after these events in kidney, kidney/pancreas, and liver transplant recipients.

Spectrophotometer and ultrasound evaluation of late toxicity following breast-cancer radiotherapy.

PURPOSE: Radiation-induced normal-tissue toxicities are common, complex, and distressing side effects that affect 90% of patients receiving breast-cancer radiotherapy and 40% of patients post radiotherapy. In this study, the authors investigated the use of spectrophotometry and ultrasound to quantitatively measure radiation-induced skin discoloration and subcutaneous-tissue fibrosis. The study's purpose is to determine whether skin discoloration correlates with the development of fibrosis in breast-cancer radiotherapy. METHODS: Eighteen breast-cancer patients were enrolled in our initial study. All patients were previously treated with a standard course of radiation, and the median follow-up time was 22 months. The treated and untreated breasts were scanned with a spectrophotometer and an ultrasound. Two spectrophotometer parameters-melanin and erythema indices-were used to quantitatively assess skin discoloration. Two ultrasound parameters-skin thickness and Pearson coefficient of the hypodermis-were used to quantitatively assess severity of fibrosis. These measurements were correlated with clinical assessments (RTOG late morbidity scores). RESULTS: Significant measurement differences between the treated and contralateral breasts were observed among all patients: 27.3% mean increase in skin thickness (p < 0.001), 34.1% mean decrease in Pearson coefficient (p < 0.001), 27.3% mean increase in melanin (p < 0.001), and 22.6% mean increase in erythema (p < 0.001). All parameters except skin thickness correlated with RTOG scores. A moderate correlation exists between melanin and erythema; however, spectrophotometer parameters do not correlate with ultrasound parameters. CONCLUSIONS: Spectrophotometry and quantitative ultrasound are objective tools that assess radiation-induced tissue injury. Spectrophotometer parameters did not correlate with those of quantitative ultrasound suggesting that skin discoloration cannot be used as a marker for subcutaneous fibrosis. These tools may prove useful for the reduction of radiation morbidities and improvement of patient quality of life.