Harvey Greenberg

Measurement of fatigue in cancer patients: development and validation of the Fatigue Symptom Inventory.

Although fatigue is one of the most common and debilitating symptoms experienced by cancer patients, it has received little systematic attention. This situation is due in large part to the lack of adequate instruments to measure fatigue. The primary aim of this study was to validate a newly developed measure of fatigue for use with cancer patients: the Fatigue Symptom Inventory (FSI). This 13 item self-report measure was designed to measure the intensity and duration of fatigue and its impact on quality of life. The psychometric properties of the FSI were assessed in women undergoing treatment for breast cancer, women who had completed treatment for breast cancer and women with no history of cancer. A seven-item interference subscale was found to have good internal consistency, with α coefficients above 0.90 in all three groups. The complete FSI was found to have rather weak to moderate test-retest reliability among patients in active treatment and healthy comparison subjects assessed on three separate occasions. Convergent validity was demonstrated using comparisons with existing measures of fatigue. Construct validity was demonstrated using comparisons between and within groups as well as comparisons with measures of anxiety and depression. Overall, the FSI was established as a valid and reliable measure of fatigue in cancer patients and healthy individuals. Suggestions are made for the potential application of the measure in clinical research.

A randomized phase III study of accelerated hyperfractionation versus standard in patients with unresected brain metastases: a report of the Radiation Therapy Oncology Group (RTOG) 9104.

PURPOSE To compare 1-year survival and acute toxicity rates between an accelerated hyperfractionated (AH) radiotherapy (1.6 Gy b.i.d.) to a total dose of 54.4 Gy vs. an accelerated fractionation (AF) of 30 Gy in 10 daily fractions in patients with unresected brain metastasis. METHODS AND MATERIALS The Radiation Therapy Oncology Group (RTOG) accrued 445 patients to a Phase III comparison of accelerated hyperfractionation vs. standard fractionation from 1991 through 1995. All patients had histologic proof of malignancy at the primary site. Brain metastasis were measurable by CT or MRI scan and all patients had a Karnofsky performance score (KPS) of at least 70 and a neurologic function classification of 1 or 2. For AH, 32 Gy in 20 fractions over 10 treatment days (1.6 Gy twice daily) was delivered to the whole brain. A boost of 22.4 Gy in 14 fractions was delivered to each lesion with a 2-cm margin. RESULTS The average age in both groups was 60 years; nearly two-thirds of all patients had lung primaries. Of the 429 eligible and analyzable patients, the median survival time was 4.5 months in both arms. The 1-year survival rate was 19% in the AF arm vs. 16% in the AH arm. No difference in median or 1-year survival was observed among patients with solitary metastasis between treatment arms. Recursive partitioning analysis (RPA) classes have previously been identified and patients with a KPS of 70 or more, a controlled primary tumor, less than 65 years of age, and brain metastases only (RPA class I), had a 1-year survival of 35% in the AF arm vs. 25% in the AH arm (p = 0.95). In a multivariate model, only age, KPS, extent of metastatic disease (intracranial metastases only vs. intra- and extracranial metastases), and status of primary (controlled vs. uncontrolled) were statistically significant (at p < 0.05). Treatment assignment was not statistically significant. Overall Grade III or IV toxicity was equivalent in both arms, and one fatal toxicity at 44 days secondary to cerebral edema was seen in the AH arm. CONCLUSION Although a previous RTOG Phase I/II report had suggested a potential benefit in patients with limited metastatic disease, a good Karnofsky performance status, or neurologic function when treated with an AH regimen, this randomized comparison could not demonstrate any improvement in survival when compared to a conventional regimen of 30 Gy in 10 fractions. Therefore, this accelerated hyperfractionated regimen to 54.4 Gy cannot be recommended for patients with intracranial metastatic disease.

Radiotherapy for cancer patients aged 80 and older : A study of effectiveness and side effects

PURPOSE To profile cancer patients aged 80 and older undergoing radiotherapy and to study the tumor response and side effects of therapy. METHODS AND MATERIALS We retrospectively analyzed the records of patients aged 80 and older who received radiation therapy at James A. Haley Veterans Hospital and H. Lee Moffitt Cancer Center between 1988 and 1995. A total of 203 patients aged 80-94 received radiotherapy during this period. Treatment sites included head and neck [50], breast [16], chest [37], pelvis [53], and miscellaneous [39]. Age, treatment site, field size, total dose, response to treatment, treatment interruptions, incidence and severity of weight loss, myelosuppression, diarrhea, mucositis, dermatitis, and follow-up status are assessed using our departmental records and hospital tumor registry. RESULTS Of 191 patients evaluated, 179 (94%) completed the treatment without serious complications. A total of 195 sites were irradiated. Twelve patients (6%) required interruption of the treatment. Therapeutic responses were seen in 86 out of 112 patients (77%) treated with curative intent (with 67% complete response) and in 67 out of 83 patients (81%) treated with palliative intent. The causes of treatment interruptions included weight loss from diarrhea, dysphagia, and progressive disease. Treatment interruptions were more likely in patients treated with large treatment fields. In patients treated for upper aero-digestive tract cancer, Grade 3 and 4 mucositis was noted in 20 and 2% of patients, respectively. Grade 1 and 2 enteritis was noted in 43% of patients treated for pelvic malignancies. Grade 3 dermatitis was noted only in 2% of patients. CONCLUSION Radiotherapy is highly effective and well tolerated by the oldest old. Age is not a contraindication to aggressive radiotherapy.

Comparison of supervised MRI segmentation methods for tumor volume determination during therapy

Two different multispectral pattern recognition methods are used to segment magnetic resonance images (MRI) of the brain for quantitative estimation of tumor volume and volume changes with therapy. A supervised k-nearest neighbor (kNN) rule and a semi-supervised fuzzy c-means (SFCM) method are used to segment MRI slice data. Tumor volumes as determined by the kNN and SFCM segmentation methods are compared with two reference methods, based on image grey scale, as a basis for an estimation of ground truth, namely: (a) a commonly used seed growing method that is applied to the contrast enhanced T1-weighted image, and (b) a manual segmentation method using a custom-designed graphical user interface applied to the same raw image (T1-weighted) dataset. Emphasis is placed on measurement of intra and inter observer reproducibility using the proposed methods. Intra- and interobserver variation for the kNN method was 9% and 5%, respectively. The results for the SFCM method was a little better at 6% and 4%, respectively. For the seed growing method, the intra-observer variation was 6% and the interobserver variation was 17%, significantly larger when compared with the multispectral methods. The absolute tumor volume determined by the multispectral segmentation methods was consistently smaller than that observed for the reference methods. The results of this study are found to be very patient case-dependent. The results for SFCM suggest that it should be useful for relative measurements of tumor volume during therapy, but further studies are required. This work demonstrates the need for minimally supervised or unsupervised methods for tumor volume measurements.

Impact of Hot Flashes on Quality of Life Among Postmenopausal Women Being Treated for Breast Cancer

Hot flashes are among the most commonly reported symptoms among women who have completed treatment for breast cancer. Relatively little is known, however, about hot flashes among women while they are undergoing breast cancer treatment. The present study investigated the prevalence and severity of hot flashes of women during chemotherapy and radiotherapy for breast cancer. We also sought to identify the medical, demographic, and treatment correlates of hot flashes during treatment and to document the impact of hot flashes on quality of life. Seventy postmenopausal women with breast cancer completed a self-report questionnaire packet during chemotherapy and radiotherapy. Forty percent (n = 28) reported hot flashes during the week prior to assessment. Of the 28 women endorsing hot flashes, 25% (n = 7) rated them as severe, 39% (n = 11) rated them as moderate, and 36% (n = 10) rated them as mild. Women with hot flashes were significantly (p < 0.05) younger and reported significantly (p < 0.001) more fatigue, poorer sleep quality, and poorer physical health compared to women without hot flashes. Multivariate analyses revealed that, even after controlling for relevant medical, demographic, and treatment variables, the prevalence of hot flashes significantly (p < 0.05) predicted poorer sleep quality, more fatigue, and worse physical health. The results indicate that hot flashes are experienced by a sizable percentage of postmenopausal breast cancer patients as they undergo treatment. Hot flashes during cancer treatment appear to have a negative impact upon patient quality of life that may be due, in part, to fatigue and interference with sleep. Future research should seek to evaluate interventions to relieve hot flashes during breast cancer treatment as a means of improving patient quality of life.

Radiation therapy in the treatment of aggressive fibromatoses

Abstract Twelve patients with aggressive but histologically benign connective tissue tumors (nine desmoids and three neurofibromas) were treated with either radiation or radiation plus surgery. Long term local control was accomplished in eight of nine desmoid tumors and 2 of 3 neurofibromas. In the successfully treated patients, local control was obtained with minimal long term complications when compared with radical surgical procedures that would have been necessary for cure. Details of radiation treatment are discussed along with proposed indications for therapy.

MONITORING BRAIN TUMOR RESPONSE TO THERAPY USING MRI SEGMENTATION

The performance evaluation of a semi-supervised fuzzy c-means (SFCM) clustering method for monitoring brain tumor volume changes during the course of routine clinical radiation-therapeutic and chemo-therapeutic regimens is presented. The tumor volume determined using the SFCM method was compared with the volume estimates obtained using three other methods: (a) a k nearest neighbor (kNN) classifier, b) a grey level thresholding and seed growing (ISG-SG) method and c) a manual pixel labeling (GT) method for ground truth estimation. The SFCM and kNN methods are applied to the multispectral, contrast enhanced T1, proton density, and T2 weighted, magnetic resonance images (MRI) whereas the ISG-SG and GT methods are applied only to the contrast enhanced T1 weighted image. Estimations of tumor volume were made on eight patient cases with follow-up MRI scans performed over a 32 week interval during treatment. The tumor cases studied include one meningioma, two brain metastases and five gliomas. Comparisons with manually labeled ground truth estimations showed that there is a limited agreement between the segmentation methods for absolute tumor volume measurements when using images of patients after treatment. The average intraobserver reproducibility for the SFCM, kNN and ISG-SG methods was found to be 5.8%, 6.6% and 8.9%, respectively. The average of the interobserver reproducibility of these methods was found to be 5.5%, 6.5% and 11.4%, respectively. For the measurement of relative change of tumor volume as required for the response assessment, the multi-spectral methods kNN and SFCM are therefore preferred over the seedgrowing method.

Breast irradiation in the older woman: a toxicity study.

Objective: To establish the tolerance of breast irradiation by women aged 65 and older.

Fatigue and Quality of Life Following Radiotherapy for Breast Cancer: A Comparative Study

Clinical reports suggest that fatigue is a common and disruptive long-term side effect of radiotherapy; however, there has been little systematic attention given to this phenomenon. The primary aim of this study was to assess fatigue its impact on quality of life in women who had completed radiotherapy for breast cancer. A key feature of this study was the inclusion of a comparison group of women of similar age with no history of cancer. The results indicated that the fatigue experienced by women after radiotherapy for breast cancer was not significantly different in intensity, duration, or disruptiveness from fatigue experienced by healthy women. In addition, radiotherapy recipients reported a quality of life similar to that of the healthy women. For both groups of women greater fatigue was related to a poorer quality of life. These findings suggest that following radiotherapy for breast cancer, women can expect to experience fatigue which is not worse than what they might “normally” experience. This information may be a useful part of psychoeducational interventions designed for women scheduled to begin radiotherapy for breast cancer.

A prospective trial of accelerated radiotherapy in the postoperative treatment of high-risk squamous cell carcinoma of the head and neck☆

PURPOSE To evaluate the feasibility and toxicity of accelerated fractionation in the postoperative setting in high risk squamous cell carcinoma of the head and neck. METHODS AND MATERIALS Thirty-two patients with high risk pathologic features (e.g., extracapsular extension, positive margins, > or = 4 nodes positive, perineural invasion) were enrolled in an accelerated fractionation schedule, using a modification of the M.D. Anderson concomitant boost technique delivering 63 Gy in 5.3 weeks at 1.8 Gy per fraction. RESULTS Thirty patients (94%) completed treatment per protocol. Confluent mucositis was seen in 22 (69%) and five patients (22%) required 2 to 4 months for complete healing. Only five patients (16%) lost more than 10% of body weight. At a median follow-up of 32 months (range 22-42 months), the crude infield failure rate is 8/32 (25%). Infield recurrence was significantly associated with the interval from surgery to commencement of radiotherapy; 0/10 (0%) patients beginning radiotherapy within 4 weeks of surgery had infield failures compared to 8/22 (36%) for patients beginning radiotherapy more than 4 weeks after surgery (p = 0.035). CONCLUSION While acute side effects appear to be increased compared to conventional radiotherapy, we conclude that postoperative accelerated radiotherapy is feasible and has acceptable toxicity in this population. These results support the concept of rapid tumor repopulation after resection. A randomized multi-institutional trial is currently underway to compare conventional and accelerated fractionation in the postoperative setting.