Weeks Of Radiation Treatment Research Articles

Detectability and intra-fraction motion of individual elective lymph nodes in head and neck cancer patients on the Magnetic Resonance Image guided linear accelerator

Background and purposeIndividual elective lymph node irradiation instead of elective neck irradiation is a new concept for head-and-neck cancer (HNC) patients developed for the Magnetic Resonance Image guided linear accelerator (MR-linac). To prepare this, the detectability, volume changes and intra-fraction motion of elective lymph nodes on the MR-linac was assessed. Materials and methodsA total of 15 HNC patients underwent diagnostic pre-treatment MRI. Additionally, two MR-linac scans were obtained with a 10-minute time difference in the first week of radiation treatment. Elective lymph node contours inside lymph node levels (Ib-V) were segmented on the pre-treatment MRI and the MR-linac scans and compared on number and maximal transversal diameter. Intra-fraction motion of elective lymph nodes on the MR-linac was estimated using Center of Mass (COM) distances and incremental isotropic expansion of lymph node segmentations. ResultsOf all 679 detected lymph nodes on the pre-treatment MRI, eight lymph nodes were not detectable on the first MR-linac scan and 16 new lymph nodes were detected. Lymph node diameters between the pre-treatment MRI scan and the MR-linac scan varied from −0.19 to + 0.13 mm. COM distances varied from 1.2 to 1.7 mm and lymph node contours had to be expanded with 3 mm. ConclusionsNearly all elective lymph nodes were detectable on the 1.5T MR-linac scan with no major changes in target volumes compared to the pre-treatment MRI. Simulated intra-fraction motion during the MR-linac scans was smaller than the 5-mm margin that will be used in the first elective lymph node radiation treatment.

Mood Disorder in Cancer Patients Undergoing Radiotherapy During the COVID-19 Outbreak

Introduction: Novel coronavirus (COVID-19) is having a devastating psychological impact on patients, especially patients with cancer. This work aims to evaluate mood disorders of cancer patients undergoing radiation therapy during COVID-19 in comparison with cancer patients who underwent radiation therapy in 2019.Materials and Methods: We included all the patients undergoing radiation therapy at our department in two-time points (once a week for a month in May 2019) and during the COVID-19 outbreak (in April 2020). All the patients were asked to fulfill a validated questionnaire (STAI-Y1, State trait anxiety inventory scale), the Symptom Distress thermometer (SDT) (from 0 to 10 score), and the Beck Depression Inventory v.2 (BDI-2). We took into account the COVID-19 outbreak and also sex, age, week of radiation treatment, and disease.Results: We included 458 patients (220 males and 238 females), with a median age of 64 years. STAI-Y1 median score was 40 (mean 41,3, range 19–79), whereas the median score of SDT was five and BDI-2 median score was 11. STAI-Y1, SDT, and BDI-2 were significantly correlated with the COVID-19 outbreak (p < 0,001 for all the tests), sex (p: 0,016 for STAI-Y1, p < 0.001 for SDT, p:0.013 for BDI-2), week of treatment (p: 0.012 for STAI-Y1 and p: 0.031 for SDT), and disease (p:0.015 for STAI-Y1, p < 0.001 for SDT and p:0.020 for BDI-2).Conclusions: The prevalence of mood disorders in patients undergoing radiation therapy is higher than expected and even higher during the COVID-19 outbreak. These measurements could be useful as a baseline to start medical humanities programs to decrease these scores.

Opioid therapy vs. multimodal analgesia in head and neck Cancer (OPTIMAL-HN): study protocol for a randomized clinical trial

BackgroundRadiation-induced mucositis (RIM) pain confers substantial morbidity for head and neck cancer (HNC) patients undergoing radiotherapy alone (RT) or chemoradiotherapy (CRT), often reducing treatment compliance. However, no standard currently exists for the treatment of RIM, and high dose opioid therapy, with its associated side effects and increased risk for chronic opioid use, remains the cornerstone of HNC pain management. The goal of this randomized clinical trial is to compare multimodal analgesia using analgesic medications with different mechanisms of action, to the institutional standard of opioid analgesia alone, in order to ascertain the optimal analgesic regimen for the management of RIM pain in HNC patients.MethodsIn this open-label, single-institution, non-inferiority, randomized clinical trial, sixty-two patients with mucosal head and neck malignancies treated with curative-intent radiation will be randomized in a 1:1 ratio, stratified by RT or CRT, between Arm 1: opioid analgesia alone as per the institutional standard, or Arm 2: multimodal analgesia using Pregabalin, Acetaminophen, and Naproxen, in addition to opioids, if required. The primary endpoint is the average 11-Numeric Rating Scale (11-NRS) score for pain during the last week of radiation treatment. Secondary endpoints include: average weekly opioid use, duration of opioid requirement, average daily 11-NRS score for pain, average weekly opioids dispensed, quality of life, hospitalizations for analgesic medication-induced complications, time to feeding tube insertion, weight loss, toxicity, treatment interruptions, and death within 3 months of completing RT treatment. Patients are eligible once analgesia is required for moderate 4/10 pain.DiscussionThis study will assess the efficacy and safety of multimodal analgesia and its impact on opioid requirements, clinical outcomes, and quality of life, as a potential new standard treatment for RIM pain in HNC patients undergoing definitive RT or CRT.Trial registrationClinicalTrials.gov Identifier: NCT04221165. Date of registration: January 9, 2020. Appendix 2 reports the World Health Organization trial registration dataset.

Effects of Low Dose Radiation on Biological Processes in Peri-tumoral and Tumoral Areas n Squamous Cell Skin Cancer

Very low dose ionizing radiation (LDR) may have paradoxically beneficial effects via an adaptive response. This adaptive response can mitigate against the potential adverse effects of high-dose radiation therapy and chemotherapy. In this study we aimed to:1.identify the specific molecular details behind the adaptive response to LDR and2.integrate the LDR adaptive response into clinical practice. Our aim was to determine how low dose radiation modifies genetic expression in both healthy and tumor tissue. To determine this, a human clinical trial (n=8) was conducted in 2018 to ascertain the biological effects of integrating 0.1Gy of LDR into standard radiotherapy (2Gy fractions) over the first two weeks of radiation treatment for epidermoid skin cancers. RNA was obtained from skin biopsies and processed for genetic expression using Affymetrix Human gene chips Clarion-D (138K genes). 8 patients with squamous skin cancer, were studied according to the experimental design showed in Figure 1. Biopsy samples were collected and total RNA preparation (100 ng), labeled cRNA synthesis, hybridization, scanning, and image analysis were performed. Changes in biological response were measured using Affymetrix microarrays. Experiments 17F1 and 17F2 were performed in duplicate, and experiments 18F3 and 18F4 were performed in triplicate. Pathway analysis was performed using the Affymetrix Transcriptome Analysis Console software and the Wikipaths database. Comparisons were performed as noted in Table 1. The difference in gene expression in healthy tissues due to LDR exposure is quite low (only 325 genes, mostly downregulated) as noted in Figures 2A and 3A and Tables 2 and 3. The 20 most important biological processes enriched are shown in Figure 4 and include Senescence and Autophagy in malignant cells, and the Genotoxicity Pathway (both downregulated). The difference in gene expression in tumor tissue due to LDR exposure is significantly more pronounced (5,651 genes, mostly upregulated) as noted in Figures 2C and 3C. The 20 most important biological processes enriched are shown in Figures 5 and 6 and Tables 4-6, and include the Allograft rejection pathway in skin cancer (upregulated). Our results suggest that very low doses of radiation (0.1Gy) have a narrow effect on gene expression when applied in the healthy peritumoral area. Down regulated genes predominate, and DNA repair mechanisms are stimulated by the first low dose in healthy tissue.

A DNA Repair-Based Model of Cell Survival with Important Clinical Consequences.

This work provides a description of a new interaction, cross-section-based model for radiation-induced cellular inactivation, sublethal damage, DNA repair and cell survival, with the ability to more accurately elucidate different radiation-response phenomena. The principal goal of this work is to describe the damage-induction cross sections, as well as repair and survival, as Poisson processes with two main types of damage: mild damage that can be rapidly handled by the most basic repair processes; and more complex damage requiring longer repair times and the high-fidelity homologous recombination (HR) repair process to ensure accuracy and safety in the survival. This work is unique in its use of Poisson statistics to quantify the main repairable cell compartments that are exposed to simple and more complex sublethal hits, the cross section of which determines what is homologically and non-homologically repairable. The new method is applied to central radiation damage and survival data, such as in vitro cellular repair and survival with key DNA repair genes knocked out, low-dose hypersensitivity (LDHS), change in survival over the cell cycle, and variation with linear energy transfer (LET) for densely ionizing ions, all results supporting our basic assumptions. Among the results, it was shown that less than 1% of the simple DSBs are lethal at approximately 2 Gy and below for sparsely ionizing radiations, but their δ-electron track ends of between 1.5 and 0.5 keV can deliver 0.5 MGy to a few hundred nm3 volumes, mainly due to multiple scatter detours and multiple secondary electrons. They can cause dual double-strand breaks (DSBs) on the periphery of nucleosomes that are the most common multiply damaged sites, with an average of 1-2 δ-electron track ends per cell nucleus at 2 Gy. LDHS is most likely due to the normal lack of fast, efficient repair of sublethal damage below approximately 0.5 Gy, and requires largely intact key DNA repair genes to achieve significant repair recovery at higher doses. The new repair model describes this phenomenon quite accurately. Cells with key non-homologous end joining (NHEJ) genes knocked-out, lose LDHS but provoke HR repair, and cells with HR genes knocked out may lose some LDHS, but provoke NHEJ repair. The DNA duplication during the S phase results in a direct doubling as well of the total and sublethal hit cross sections. For the lowest LET carbon ions, NHEJ is reduced to where it is almost eliminated at maximum relative biological effectiveness (RBE), while HR is induced more than by X rays, due to complex damage and misrepair of DSBs produced by numerous δ electrons. The use of a lower LET such as electrons or photons during the final week of radiation treatment may potentially maximize complication-free cure. Optimally-designed weekly fractionation schedules are proposed to maximize the DNA repair potential in normal tissues. Additionally, the optimal therapeutic ion species, LET, apoptosis and permanent growth arrest/senescence window is identified with helium, lithium and boron ions and LETs at approximately 15-55 eV/nm, to maximize these quantities in the tumor and minimize them in the normal tissues, resulting in a very high probability of complication-free cure.

Radiotherapy Radio protective effect of 2- deoxy D-glucose with combination of selective antioxidant medicinal plant Vitis vinifera, Camellia sinensis, and Zingiber officinale extracts in mice

High doses of radiation therapy are used to destroy cancer cells, these high doses of radiations also damage healthy cells and tissues near the treatment area or whole body. At present, major advances of radiation therapy have made it more precise, leading to fewer side effects. The side effects often start during second week of radiation treatment So it is necessary to minimize these side effects with natural available medication. Previous studies shown that, 2- deoxy D- glucose, an analogue of glucose and glycolytic inhibitor, enhances radiation induced damage, selectively in tumour cells while protecting normal cells suggest that 2- deoxy D- glucose can be used as a differential radio modifier to improve the efficacy of radiotherapy and also it is shown that antioxidant medicinal plants like vitis Vinifera, camellia Sinensis, and zingiber officinale have shown protective effect against radiation induced damage in previous studies. So in the present study, we have selected these antioxidant medicinal plant extracts combines with 2- deoxy D- glucose as a treatment, before and after radiation therapy and measured the levels of nitric oxide, lipid peroxidation and antioxidant enzymes like superoxide dismutase, catalase and glutathione peroxidase in tissues like blood, liver, kidney and brain tissues of mice after completion of study. In the present study, it is found that the highest effect is found in a group of animals which are on combination of normal diet and feeding of deoxy – D glucose with grape seed extract, green tea extract and ginger extract in proportion of 1:1:1, in this group of animal’s radiation induced micronucleus formation, formation of metamyelocytes and dysplastic myeloid series cells formation is also found significantly decreased.

Building Family Caregiver Skills Using a Simulation-Based Intervention: A Randomized Pilot Trial.

To evaluate the feasibility, acceptability, safety, and fidelity of a psychoeducational intervention to improve family caregiver technical and communication skills using structured simulations. 18 family caregivers of adult patients receiving radiation therapy for head and neck cancer at University Hospitals Seidman Cancer Center in Cleveland, Ohio. A two-group, randomized pilot trial design was used. The intervention consisted of four one-on-one sessions between the caregiver and nurse interventionist during the patient's first, second, fourth, and sixth week of radiation treatment. Participants completed measures of self-efficacy for caregiving, anxiety, depression, and health-related quality of life at baseline, during the fifth week of radiation therapy, and four weeks after radiation therapy. 4 of the 9 caregiver participants completed the intervention. Improvements in scores for the intervention group were noted for self-efficacy, global mental health, anxiety, and depression. Refinement of the intervention is needed to improve feasibility. Although a caregiver intervention that incorporates simulation for skills training is acceptable and safe, flexibility in protocol is needed.

MELADERM-trial: Melatonin cream against acute radiation dermatitis in patients with early breast cancer

Radiation&#x0D; dermatitis following radiation therapy in the treatment of early breast cancer&#x0D; can lead to discontinuation or prolongation of treatment and an impaired&#x0D; quality of life. Melatonin has been demonstrated to protect against radiation&#x0D; injury. The aim of this study is to investigate whether melatonin can protect&#x0D; against radiation dermatitis when applied topically in women receiving&#x0D; radiation therapy for early breast cancer. This study will be a randomized,&#x0D; placebo-controlled, double-blind controlled trial. Patients will apply the&#x0D; melatonin or placebo preparation topically twice daily for the duration of&#x0D; their radiation therapy. Our objective outcomes will be the Radiation Therapy&#x0D; Oncology Group’s acute radiation morbidity scoring criteria for skin, image&#x0D; analysis of clinical photographs, and use of steroid cream for radiation&#x0D; dermatitis. Subjective outcomes will be quality of life questionnaires&#x0D; developed by the European Organisation for Research and Treatment of Cancer.&#x0D; Outcomes will be measured throughout the five weeks of radiation treatment and&#x0D; be followed up for another three weeks. According to sample-size calculations&#x0D; and inclusion schedule, we intend to include a total of 80 evaluable patients. We&#x0D; will analyze the primary outcomes using parametric and non-parametric tests&#x0D; where applicable. Secondary outcomes will be analyzed by a mixed linear model. Most&#x0D; patients with breast cancer who undergo radiation therapy will develop&#x0D; radiation dermatitis as a result of the therapy. Should our intervention&#x0D; provide better outcomes, many patients could obtain a better quality of life.&#x0D; We expect topical melatonin treatment to have little or no adverse effects, to&#x0D; be easy to apply, and not to interfere with the anti-tumor efficacy of the&#x0D; radiation therapy.

Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial

Both perioperative chemotherapy and postoperative chemoradiotherapy improve survival in patients with resectable gastric cancer from Europe and North America. To our knowledge, these treatment strategies have not been investigated in a head to head comparison. We aimed to compare perioperative chemotherapy with preoperative chemotherapy and postoperative chemoradiotherapy in patients with resectable gastric adenocarcinoma. In this investigator-initiated, open-label, randomised phase 3 trial, we enrolled patients aged 18 years or older who had stage IB- IVA resectable gastric or gastro-oesophageal adenocarcinoma (as defined by the American Joint Committee on Cancer, sixth edition), with a WHO performance status of 0 or 1, and adequate cardiac, bone marrow, liver, and kidney function. Patients were enrolled from 56 hospitals in the Netherlands, Sweden, and Denmark, and were randomly assigned (1:1) with a computerised minimisation programme with a random element to either perioperative chemotherapy (chemotherapy group) or preoperative chemotherapy with postoperative chemoradiotherapy (chemoradiotherapy group). Randomisation was done before patients were given any preoperative chemotherapy treatment and was stratified by histological subtype, tumour localisation, and hospital. Patients and investigators were not masked to treatment allocation. Surgery consisted of a radical resection of the primary tumour and at least a D1+ lymph node dissection. Postoperative treatment started within 4-12 weeks after surgery. Chemotherapy consisted of three preoperative 21-day cycles and three postoperative cycles of intravenous epirubicin (50 mg/m2 on day 1), cisplatin (60 mg/m2 on day 1) or oxaliplatin (130 mg/m2 on day 1), and capecitabine (1000 mg/m2 orally as tablets twice daily for 14 days in combination with epirubicin and cisplatin, or 625 mg/m2 orally as tablets twice daily for 21 days in combination with epirubicin and oxaliplatin), received once every three weeks. Chemoradiotherapy consisted of 45 Gy in 25 fractions of 1·8 Gy, for 5 weeks, five daily fractions per week, combined with capecitabine (575 mg/m2 orally twice daily on radiotherapy days) and cisplatin (20 mg/m2 intravenously on day 1 of each 5 weeks of radiation treatment). The primary endpoint was overall survival, analysed by intention-to-treat. The CRITICS trial is registered at ClinicalTrials.gov, number NCT00407186; EudraCT, number 2006-004130-32; and CKTO, 2006-02. Between Jan 11, 2007, and April 17, 2015, 788 patients were enrolled and randomly assigned to chemotherapy (n=393) or chemoradiotherapy (n=395). After preoperative chemotherapy, 372 (95%) of 393 patients in the chemotherapy group and 369 (93%) of 395 patients in the chemoradiotherapy group proceeded to surgery, with a potentially curative resection done in 310 (79%) of 393 patients in the chemotherapy group and 326 (83%) of 395 in the chemoradiotherapy group. Postoperatively, 233 (59%) of 393 patients started chemotherapy and 245 (62%) of 395 started chemoradiotherapy. At a median follow-up of 61·4 months (IQR 43·3-82·8), median overall survival was 43 months (95% CI 31-57) in the chemotherapy group and 37 months (30-48) in the chemoradiotherapy group (hazard ratio from stratified analysis 1·01 (95% CI 0·84-1·22; p=0·90). After preoperative chemotherapy, in the total safety population of 781 patients (assessed together), there were 368 (47%) grade 3 adverse events; 130 (17%) grade 4 adverse events, and 13 (2%) deaths. Causes of death during preoperative treatment were diarrhoea (n=2), dihydropyrimidine deficiency (n=1), sudden death (n=1), cardiovascular events (n=8), and functional bowel obstruction (n=1). During postoperative treatment, grade 3 and 4 adverse events occurred in 113 (48%) and 22 (9%) of 233 patients in the chemotherapy group, respectively, and in 101 (41%) and ten (4%) of 245 patients in the chemoradiotherapy group, respectively. Non-febrile neutropenia occurred more frequently during postoperative chemotherapy (79 [34%] of 233) than during postoperative chemoradiotherapy (11 [4%] of 245). No deaths were observed during postoperative treatment. Postoperative chemoradiotherapy did not improve overall survival compared with postoperative chemotherapy in patients with resectable gastric cancer treated with adequate preoperative chemotherapy and surgery. In view of the poor postoperative patient compliance in both treatment groups, future studies should focus on optimising preoperative treatment strategies. Dutch Cancer Society, Dutch Colorectal Cancer Group, and Hoffmann-La Roche.

FDG-PET Imaging and Assessment of Tumor Dose Response (SF2) Distribution

To derive tumor cell survival fraction after 2 Gy (SF2) distribution from multiple FDG-PET images obtained during the early weeks of radiotherapy, and evaluate the predictability of SF2 distribution on tumor local failure and recurrent location. FDG-PET/CT images with PET image voxel size of 4 x 4 x 4 mm3 obtained at the pre, weekly and 3/6 months post chemo-radiation treatment for each of 18 HN cancer patients were used for the study. Four of the 18 patients had biopsy proven local failure (22.2%) with the median follow-up time 22.2 (7.5 ∼ 43.3) months. All weekly and post-treatment PET/CT images of each patient were registered voxel by voxel to the pre-treatment planning PET/CT image. Tumor dose response marker, SF2(v), for each tumor voxel v was derived using the linear regression on the logarithm of the first 4 weekly tumor metabolic ratios defined as lnTMRi(v) = ln(SUVi(v)/SUV0(v)), i = 1 to 4. Sensitivity and specificity of SF2-Volume parameters on the prediction of local tumor control and failure were calculated. The relationship between a locally recurrent tumor volume and radio-resistant tumor volume was evaluated. The locally recurrent tumor volume was defined as the iso-SUV volume formed using the %SUVmax on the post-treatment PET image, while the radio-resistant tumor volume was created using the tumor voxels with SF2 > 0.9. The inter- and intra-tumor heterogeneities of SF2 distribution were large with the individual mean from 0.56 to 0.89, and the individual STD from 0.08 to 0.16. All failures had either large mean SF2 or large STD. Sensitivity and specificity, as well as the accuracy, of using V(SF2 > x) to predict treatment local failure were listed in Table 1. Tumor sub-volume with SF2 > 0.9 shows highly predictability on tumor local recurrence after the standard chemo-radiotherapy. In addition, Tumor local recurrent volume (defined using the 70, 80, or 90% of the Post-SUVmax) always contains the radio-resistant tumor voxels (Table 1). Tumor voxel dose response SF2 can be derived using multiple FDG-PET imaging obtained during the early weeks of radiation treatment. Distribution of SF2 has significant predictability power on tumor local failure, and the recurrent location. It can be used as the objective function to target radio-resistant tumor cells.Abstract 1062; Table 1Tumor Volume(SF2>x)V(SF2>0.9)V(SF2>1.0)V(SF2>1.1)Sensitivity0.751.01.0Specificity1.01.01.0Accuracy0.941.01.0AUC0.961.01.0P-value0.0030.0020.002Optimal Cutoff (cc)4.620.960.14Locally Recurrent Volume (LRV)(CC)70% Post-SUVmax 1.09 ∼ 2.8280% Post-SUVmax 0.58 ∼ 1.1590% Post-SUVmax 0.2 ∼ 0.45Radio-Resistant Volume in LRV(CC)0.7 ∼ 1.340.38 ∼ 0.70.19 ∼ 0.38 Open table in a new tab

The Effect of Reflexology on the Pain-Insomnia-Fatigue Disturbance Cluster of Breast Cancer Patients During Adjuvant Radiation Therapy

To evaluate the effects of reflexology treatment on quality of life, sleep disturbances, and fatigue in breast cancer patients during radiation therapy. A total of 72 women with breast cancer (stages 1-3) scheduled for radiation therapy were recruited. Women were allocated upon their preference either to the group receiving reflexology treatments once a week concurrently with radiotherapy and continued for 10 weeks or to the control group (usual care). The Lee Fatigue Scale, General Sleep Disturbance Scale, and Multidimensional Quality of Life Scale Cancer were completed by each patient in both arms at the beginning of the radiation treatment, after 5 weeks, and after 10 weeks of reflexology treatment. The final analysis included 58 women. The reflexology treated group demonstrated statistically significant lower levels of fatigue after 5 weeks of radiation therapy (p < 0.001), compared to the control group. It was also detected that although the quality of life in the control group deteriorated after 5 and 10 weeks of radiation therapy (p < 0.01 and p < 0.05, respectively), it was preserved in the reflexology group, which also demonstrated a significant improvement in the quality of sleep after 10 weeks of radiation treatment (p < 0.05). Similar patterns were obtained in the assessment of the pain levels experienced by the patients. The results of the present study indicate that reflexology may have a positive effect on fatigue, quality of sleep, pain, and quality of life in breast cancer patients during radiation therapy. Reflexology prevented the decline in quality of life and significantly ameliorated the fatigue and quality of sleep of these patients. An encouraging trend was also noted in amelioration of pain levels.

Differences in quality of life in obese and normal weight head and neck cancer patients undergoing radiation therapy.

The aim of this study was to evaluate health-related quality of life (HRQOL) in patients with different body mass indices (BMI, <25 vs ≥25) undergoing radiation treatment for head and neck cancer. HRQOL was examined by the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and the EORTC QLQ-H&N35, in the beginning and in the end of radiation treatment in 60 patients treated at University Hospital in Northern Norway. Information about nutritional status with weight loss, hemoglobin level (Hb), serum albumin, and a study-specific questionnaire also was filled out in the beginning and in the end of treatment. The patients' general condition, skin, and mucous membranes (CTCAE v.3.0) (grades 1 to 5 with unique clinical descriptions) were documented four times during radiation treatment. Changes in HRQOL were calculated and compared by paired sample t test. Multiple regression analyses were used to examine correlations between baseline BMI and changes in HRQOL, CTCAE v.3.0 toxicity, nutritional status, and information that radiotherapists provided to patients. Patients with BMI ≥ 25 had less mucosal changes after 2 weeks of radiation treatment than patients with BMI < 25 (p = 0.010). Differences regarding feeding tube use (p = 0.037) and intake of nutritional supplements before radiation treatment (p = 0.001) were also seen. Patients with overweight had more dyspnea (p = 0.033) before treatment and more problems with dry mouth (p = 0.042) after treatment. During treatment, patients with BMI ≥ 25 had more problems with opening mouth (p = 0.034) than patients with BMI < 25 and more changes in sexuality (p = 0.019). Patients with BMI ≥ 25 received less information about food and drink (p = 0.011) in the radiation treatment period than normal weight patients. BMI influences HRQOL and toxicity. Additional longitudinal studies should examine whether or not overweight patients persistently experience more problems with dry mouth and opening their mouth. Regardless of BMI, all patients should be informed about nutritional recommendations during treatment.

Random control clinical trial on the effects of aerobic exercise training on erythrocyte levels during radiation treatment for breast cancer

Erythrocyte changes from aerobic exercise training were examined during radiation treatment of breast cancer. Twenty sedentary females with breast carcinoma who were ages 35 to 65 years were randomized to aerobic exercise (AE) of walking for 20 to 45 minutes, 3 to 5 times per week, at 50% to 70% of measured maximum heart rates or to placebo stretching (PS) activities 3 to 5 days per week during 7 weeks of radiation treatment. Measures were obtained 1 week before and after the radiation regimen. Serum blood analyses, through complete blood counts, measured red blood cell counts (RBC), hematocrit (HCT), and hemoglobin (HB). Peak aerobic capacity (peak VO(2)) was measured by exercise testing with oxygen uptake analysis to assess training. A Wilcoxon Mann-Whitney U test examined changes between groups (P < or = .05 for significance). AE peak VO(2) increased by 6.3% (P = .001) and PS decreased by 4.6% (P = .083). RBC increased in AE from 4.10 to 4.21 million cells/microL and declined in PS from 4.30 to 4.19 million cells/microL; the between-group differences were significant (P = .014). HCT increased in AE from 38.0% to 38.8% and declined in PS from 37.40% to 36.50%; the between-group differences were significant (P = .046). HB increased in AE from 12.3 to 12.4 g/dL and declined in PS from 12.25 to 11.77 g/dL; the between-group differences were significant (P = .009). The results of the current study suggest that moderate intensity aerobic exercise appears to maintain erythrocyte levels during radiation treatment of breast cancer compared with the declines observed in nontraining individuals. These findings suggest a safe, economical method to improve fitness and maintain erythrocytes in women during radiation treatment of breast cancer.

Randomized trial of yoga in women with breast cancer undergoing radiation treatment

8505 Background: Yoga, an ancient Indian science, incorporates stress-reduction techniques that include regulated breathing, visual imagery, and meditation, as well as various postures that may be useful for cancer patients. Methods: A yoga program was developed that including loosening and breathing exercises, postures, alternate nostril breathing, a deep relaxation technique, and meditation for patients with breast cancer who were undergoing radiotherapy. Women participated in bi-weekly classes during their 6 weeks of radiation treatment. Sixty-one women with breast cancer were randomly assigned to either the yoga program or to a waitlist control group. Patients completed measures of intrusive thoughts and avoidance behaviors (Impact of Events Scale: IES), depressive symptoms (CES-D), sleep disturbances (Pittsburgh Sleep Quality Index), fatigue (BFI), and quality of life (SF-36) at baseline, 1 week, and 1 and 3 months after the last radiation therapy. We report on the outcomes 1 week after the end of radiotherapy. Results: The average age of the women was 52, 3% stage 0, 28% stage I, 43% stage II, and 26% stage III, 48% had undergone breast-conserving surgery, and 75% had received chemotherapy prior to starting radiotherapy. Analysis of covariance, controlling for baseline, revealed that the yoga group had significantly better SF-36 physical function scores (adjusted means: yoga 81.8 vs. control 68.6, P &lt; 0.01), significantly higher SF-36 general health scores (adjusted means: yoga 78.3 vs. control 67.9, P &lt; 0.03), marginally better SF-36 social functioning scores (adjusted means: yoga 85.3 vs. control 76.0, P &gt; 0.1), significantly lower levels of sleep-related daytime dysfunction (adjusted means: yoga 0.5 vs. control 1.2, P &lt; 0.04), and marginally lower levels of fatigue (adjusted means: yoga 1.9 vs. control 3.1, P &lt; 0.06) than the control group. There were no other group differences on the SF-36 subscales or for the CES-D or IES scores. Conclusions: The results indicated that the yoga program was associated with statistically and clinical significant improvements in aspects of quality of life. No significant financial relationships to disclose.

Quality of life impact of early radiation treatment for breast cancer

Accelerated partial breast radiotherapy is a treatment modality that may offer tumor control similar to traditional breast radiotherapy while reducing the burden of therapy. Evaluation of the importance of such an advance requires measurement of patient preference and tolerance for the side effects of early treatment. In our study, we evaluated patient-reported quality of life for women early in their radiation treatment for breast cancer. Breast cancer patients undergoing radiation treatment at Northwestern Memorial Hospital were recruited for participation in the study. All patients receiving radiation treatment for breast cancer were considered eligible. After obtaining informed consent, a baseline interview was conducted with each patient during the first week of radiation therapy, and a second interview was conducted during the second week of therapy. Participants completed multiple outcome measures at each interview. The ECOG performance status is a general measure of patient function. The FACT-B poses specific questions to the patients about aspects of their well-being. Four of the subscales are designed to generalize to all cancer patients, and the fifth addresses specific concerns for women with breast cancer. Standard gamble and time trade-off utility questionnaires were also administered. Each asks patients to think broadly about their overall quality of life, without delineation of specific factors of their well-being that might be affected by cancer or its treatment. Descriptive analyses were conducted to characterize quality of life during the first 2 weeks of radiation treatment. Changes in quality of life were analyzed using a linear regression model, to determine whether patient characteristics (baseline function, age, and living arrangements) could predict improvement or worsening of quality of life, early in radiation treatment. All statistical analyses were conducted at the alpha = 0.10 level. A total of 69 patients completed both assessments. Measures of the impact of early radiation treatment differed substantially, with patient function declining between week one and week two, measured by the ECOG performance status (p < 0.001) and quality of life remaining unchanged, when measured by four of the five domains of the FACT-B, or even increasing, when measured by the FACT-B breast cancer subscale, and by both utility measures (p < 0.01). Statistically significant predictors of change differed across the three models. Improvement in standard gamble utilities was weakly related to higher baseline ECOG performance status (no symptoms relative to some bed rest) while improvement in breast cancer subscale scores was more substantially related to lower baseline ECOG performance status (some symptoms relative to none). Improvement in time trade-off utilities was related to the presence of other adults in the home (a measure of social support). Currently there is significant interest in accelerated partial breast radiotherapy (PBRT). It has been thought that treatment delivered rapidly over one week would be more convenient and therefore have the potential to reduce treatment burden and improve overall quality of life relative to standard breast radiotherapy. This current study found a small improvement in patient-reported quality of life during the second week of standard breast radiotherapy. However, concurrent reductions in patient function were also found. The extent to which improvements in quality of life reflect adjustments in expectations of treatment effects by the patients, rather than true improvement in quality of life, has not been tested. As we move forward in the use of PBRT it is important to prospectively measure quality of life in addition to standard toxicity and efficacy

Polarity therapy and cancer-related fatigue

8147 Background: Cancer and its treatment produces fatigue in a majority of patients. Despite the very high prevalence of this problem, no effective treatments are available. Increasing numbers of cancer patients are turning to complementary and alternative medicine practices to find relief. We examined the efficacy of Polarity Therapy (PT), a massage-like intervention classified by NCCAM as an “energy therapy,” in relieving fatigue in female breast cancer patients receiving radiation therapy. Methods: 15 Patients (mean age = 52.5) were randomly assigned to one of three trial groups. Arm 1 patients did not receive any (PT). Patients assigned to Arm 2 received a PT tx on a Tuesday during their 4th week of radiation treatment. Patients assigned to Arm 3 received PT on Tuesdays during \(\underline{\mathrm{both}}\) their 4th and 5th weeks of radiation treatment. Patients completed the Brief Fatigue Inventory (BFI) during the 3rd through 5th weeks of radiation treatment. Each PT session lasted 60–75 minutes with the patient lying fully clothed on a massage table while the same experienced, licensed Polarity Therapist administered all PT treatments. Results: Change scores on the BFI from baseline showed a statistically significant improvement in fatigue in the 10 patients who had PT compared to the 5 patients who did not after the first week (mean change score: one PT tx = 1.0, SD = 1.46; no PT = −0.6, SD = .93; p = .05). Eight of the ten patients showed an improvement in fatigue following their first PT treatment, while only one of five patients in the control group had an improvement in fatigue during the same time frame. A one-way analysis of variance (ANOVA) examining group differences the following week closely approached conventional levels of statistical significance (mean change score: two PT tx = 2.2, SD = 1.03; one PT tx = 1.6, SD = 1.10; no PT = 0.6, SD = .87; p = .08. A significant (p = .03) linear contrast suggested a possible dose effect. Conclusions: This pilot supports a confirmatory trial of Polarity Therapy for cancer- related fatigue. No significant financial relationships to disclose.

The correlation between epidermal growth factor levels in saliva and the severity of oral mucositis during oropharyngeal radiation therapy

Epidermal growth factor (EGF) is present in biologic fluids, including saliva, and plays a role in maintenance of the epithelial barrier and in healing of damaged mucosa. The purpose of this study was to assess the relation between salivary EGF and the severity of oral mucositis in patients with carcinoma of the head and neck during radiation therapy. Whole resting saliva (WRS) and whole stimulated saliva (WSS) were collected prior to radiation and each week during radiation treatment for 11 men and 7 women. Oral mucositis was evaluated using the National Cancer Institute (NCI) scale of 0-4 and the Oral Mucositis Assessment Scale (OMAS), which evaluates the extent of erythema (scale of 0-2) and ulcerations (scale of 0-3) in nine oral sites. The overall OMAS score of 0-45 reflected the mucosal condition. EGF was assayed in the saliva specimens. The total mean radiation dose delivered to the head and neck was 5667 centigrays (cGy) in a mean of 24 fractions. Ulcerative oral mucositis occurred in 94% of patients. The mean OMAS score ranged from 2.83 in the first week of treatment to 14.77 in the fifth week. The mean WRS and WSS volumes decreased significantly from pretreatment to the first week of radiation treatment and then remained stable. A similar pattern was seen for the mean total output of EGF. A significant and negative correlation was found between higher levels of EGF in stimulated saliva and low OMAS score, reflecting less severe erythema and ulceration. A general trend showing that less tissue damage was associated with a higher EGF level in resting saliva also was illustrated. EGF levels were correlated with the OMAS score; however, no correlation was found when assessing the NCI score, which combines tissue damage with function and symptoms in a single score. Radiation-induced mucositis appeared to be modified by saliva volume, total EGF, and concentration of EGF in the oral environment. Saliva volume and total EGF output decreased significantly in the first weeks of treatment and remained reduced throughout radiation therapy. The findings suggest that higher levels of EGF in saliva, particularly in stimulated saliva, prior to and during radiation treatment may be associated with less severe mucosal damage due to radiation therapy. It is also postulated that human EGF may affect the development and healing of radiation-damaged mucosa.

Concomitant infusion cisplatin and hyperfractionated radiotherapy for locally advanced nasopharyngeal and paranasal sinus tumors

This is a prospective study to improve the therapeutic ratio in the treatment of patients with locally advanced nasopharyngeal and paranasal sinus tumors by using split-course concomitant infusion cisplatin chemotherapy and hyperfractionated radiotherapy. From 1983 to 1993, 21 patients with locally advanced nasopharyngeal and paranasal sinus tumors (T3 and T4, or recurrent tumors involving the facial bones and/or the base of the skull) were treated with a regimen of split-course hyperfractioned radiotherapy (1.2 Gy/fraction/bid) and concomitant infusion cisplatin (5-10 mg/m2/24 h). The therapy was given in three separate 2-week sessions with 1 to 2 week breaks between sessions. Seventeen of 21 patients were treated with curative intent with cumulative radiation doses ranging from 64.8 to 70.8 Gy. Four patients were treated with palliative intent to a total dose of less than 60 Gy or to a limited field due to previous irradiation. Sixteen of 17 patients (94%) treated curatively achieved a complete response. Of the 16 patients who achieved complete response, 7 patients (50%) were alive at the time of analysis (36 to 126 months). One patient was alive at 4 years with no evidence of disease, and died in 10 years at the age of 80 of unknown cause. Two patients died of local recurrence at 21 and 45 months and one patient died of a cerebrovascular accident at 12 months with disease status unknown. Five patients died of distant metastases. The one patient who had a partial response died in 25 months with local disease and metastases to the bone and lung. Four patients that were previously irradiated received a reduced total dose or treated to a limited irradiation field. All had near complete responses, but died within a year of treatment, with the exception of one patient who died at 23 months. Acute reactions included intense erythema of the mucosa in all patients. Five of 21 (23%) developed punctate mucositis and 3 of 21 (14%) developed confluent mucositis. Hematologically, one patient developed neutropenia (1800 WBC/mm3) and one developed thrombocytopenia (38,000/mm3). A rising creatinine was observed in three patients (2.0, 1.7, 1.7) all of whom were treated with the higher 10 mg/m2/day dose of infusional cisplatin. In all three of these cases, the creatinine slowly returned to normal over a 6-month period. Hormonal evaluations were performed in three patients and all were within normal ranges. There was no evidence of neck fibrosis or trismus. One patient with gross recurrent disease of the orbit developed blindness of the involved eye due to corneal opacification. The orbital area had been reirradiated in this patient. Concomitant infusion cisplatinum with hyperfractionated radiation improved tumor control, but did not increase normal tissue injury. Acute reactions were minimized by splitting the treatment with a 1- to 2-week break after each 2 weeks of radiation treatment. Late complications were not increased by using a hyperfractionated radiation regimen. The local failure rate was only 18% (3 of 17 patients), but the distant failure rate was 35% (6 patients). Further investigation is needed to prove if adjuvant chemotherapy after concomitant chemoradiation improves survival by decreasing the distant failure in such advanced cases.

Author reply

Wronski and Lederman suggest that the inclusion of patients with active systemic disease could have impacted on the results of our trial. Approximately 45% of the patients in our trial had extracranial metastases compared with 37.5% and 31.7%, respectively, in the 2 other published randomized trials evaluating the addition of surgery to radiotherapy in patients with a single brain metastasis.1, 2 In our trial, the two treatment groups were reasonably well-balanced in terms of the presence of extracranial metastases: 49% in the radiation alone group and 41% in the surgery plus radiation group. Hence, there is no bias in the comparison of the two groups. Furthermore, there was no statistically significant difference in survival between radiation and surgery plus radiation in patients with localized disease and in patients with extracranial metastases. We do agree that based on the results of our trial and the other two randomized trials, surgery is not warranted for patients with widespread systemic metastases. Wronski and Lederman suggest that in imbalance in histology between treatment groups could have biased the results in favor of radiation therapy. They argue that 10 patients (24%) in the surgical group had colon carcinoma, which is relatively radioresistant and that 10 patients (23%) in the radiation group had breast carcinoma, which is relatively radiosensitive. In fact, as shown in Table 1 in our article, eight patients in the radiation group had breast cancer. The most important baseline characteristic influencing survival in these patients is the presence or absence of systemic metastases, not individual histology. In fact, in our trial 21 patients in the radiation group had extracranial metastases compared with 17 patients in the surgery plus radiation group. In the analysis of a randomized trial it is usual for the length of survival to commence with the date of randomization. It is obvious that the addition of 2 weeks of radiation treatment to the radiation arm does not impact in a meaningful way on the comparison of median survivals between the two groups. It is the convention of most journals for an intention-to-treat analysis to be performed. Patients are analyzed according to what treatment arm they are randomized to, not by what treatment they actually receive. The inclusion of the ten radiation patients who received surgery in the surgery arm is inappropriate. They may have been patients with a worse prognosis and their inclusion in the surgery arm could potentially bias the results against surgery. We did consider as a worst case scenario, the occurrence of a surgical intervention as an outcome event, i.e., a failure of treatment. This analysis did not change the results of the trial with the cumulative mortality curves of the two treatment groups being superimposable (P = 0.82). The centers participating in our study are well established oncology centers with experienced neurosurgical units. Seventy-four of the 84 patients were contributed by 3 centers. There was no imbalance within centers between treatment arms. The strongest data supporting the efficacy of any treatment comes from a randomized trial.3 There are three published randomized trials evaluating radiation versus radiation plus surgery in patients with single brain metastases.1, 2, 4 We are surprised that Wronski and Lederman base much of their argument concerning potential biases on nonrandomized descriptive series that in fact are far more open to bias. Mark Levine M.D. M.Sc. F.R.C.P.(C)*

Regional blood flow in human tumours with special reference to the effect of radiotherapy

Blood flow in 41 superficial tumour nodules, of which nine were lymphomas, nine anaplastic carcinomas and 23 differentiated malignomas was measured using the 133Xe-clearance method. The lymphomas showed statistically higher blood flow (38-4 ml./min/100 g) than anaplastic (11-4 ml./min/100 g) and differentiated tumours (13-7 ml./min/100 g). After one week of radiation treatment the mean blood flow in anaplastic carcinomas was higher than the initial value. After an interval following the end of the radiation treatment the circulation diminished significantly compared with that observed immediately at the end of radiotherapy. The size of the tumours did not correlate with the blood flow.