High-dose intra-arterial cisplatin boost with hyperfractionated radiation therapy for advanced squamous cell carcinoma of the head and neck.

PURPOSE: To evaluate the tolerance and efficacy of intra-arterial (IA) cisplatin boost with hyperfractionated radiation therapy (HFX-RT) in patients with advanced squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Forty-two patients with locally advanced primary SCCHN were treated on consecutive phase I/II studies of HFX-RT (receiving a total of 76.8 to 81.6 Gy, given at 1.2 Gy bid) and IA cisplatin (150 mg/m(2) received at the start of and during RT boost treatment). RESULTS: Acute grade 3 to 4 toxicities were as follows: grade 4 and grade 3 mucosal toxicity occurred in three (7%) and 31 patients (69%), respectively, and grade 3 hematologic, infectious, and skin events occurred in one patient each. Eight of 24 patients (33%) were unable to receive a second planned dose of IA cisplatin because of general anxiety (n = 5), nausea and/or emesis (n = 2), or asymptomatic occlusion of an external carotid artery (n = 1). Thirty-seven patients (88%) experienced complete response (CR) at primary site. Twenty-nine (85%) of 34 patients presenting with nodal disease experienced CR. The actuarial 2-year rates of locoregional control and disease-specific and overall survival are 73%, 63%, and 57%, respectively, with a median active follow-up of 30 months. CONCLUSION: In this highly unfavorable subset of patients, these results seem superior to previously reported chemoradiation regimens in more favorable patients. Use of a second dose of IA cisplatin boost was associated with increased toxicity without obvious therapeutic gain. This novel strategy allows for an incremental increase in the treatment intensity of the HFX-RT regimen recently established as superior to once-a-day RT.

Adherence to recommendations for clinical follow-up after benign breast biopsy.

PURPOSE: Women who undergo a benign breast biopsy are at elevated risk for the subsequent development of breast cancer (BC). Therefore, appropriate clinical follow-up of a benign breast biopsy is important. The present study examines the extent and correlates of nonadherence with follow-up recommendations after a benign breast biopsy. METHODS: Women (n = 114) who had undergone a benign breast biopsy completed an initial telephone interview within 50 days of their biopsy (mean = 21 days). Additional telephone interviews were completed at 4 and 8 months post-biopsy. Measures of BC risk perception, general and BC-specific distress, BC-related attitudes and beliefs, social support, optimism, and informational coping style were completed. Specific recommendations for clinical follow-up and evidence of actual follow-up were obtained from medical records. RESULTS: Of 103 women given a specific recommendation for clinical follow-up, 34% were classified as nonadherent with follow-up recommendations. Logistic regression analyses indicated that nonadherent women were characterized by younger age, recommendations for follow-up by clinical breast examination alone, greater confidence in their ability to perform breast self-examination properly, higher perceived personal risk for BC, and greater BC-specific distress. CONCLUSION: Despite the importance of appropriate clinical follow-up of a benign breast biopsy, about one-third of women did not adhere to recommended follow-up. Risk factors for nonadherence suggest potential avenues for interventions to enhance participation in appropriate clinical follow-up.

High-dose intra-arterial cisplatin and concurrent hyperfractionated radiation therapy in patients with locally advanced primary squamous cell carcinoma of the head and neck: report of a phase II study.

BACKGROUND: This phase II study evaluates the tolerability and efficacy of concurrent hyperfractionated radiation therapy (HFX-RT) and high-dose intra-arterial (IA) cisplatin in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). METHODS: Between December 1995 and November 1997, 20 patients with locally advanced T4/T3 SCCHN were treated with HFX-RT (76.8-79.2 Gy at 1.2 Gy bid over 6-7 weeks) and high-dose IA cisplatin (150 mg/m(2) given at the start of RT boost treatment [start of week 6]). Seventeen patients (85%) had T4 disease, and 14 (70%) had N2/ N3 disease. RESULTS: Grade 3-5 acute toxicity was limited to one grade 4 (5%) and 14 grade 3 (70%) mucosal events. No grade 3/4 hematologic toxicity was observed. Median weight loss during therapy was 9% (range, 2%-16%). Eighteen patients had complete response (90%) at the primary site; 14 were confirmed pathologically. Among 17 patients with positive neck disease, 16 (94%) achieved complete response in the neck, including 12 of 13 patients with N2/N3 disease who underwent planned neck dissection. Active follow-up ranges from 12 to 32 months (median, 20 months) with 11 patients alive without disease, 5 dead of disease, and 4 dead of intercurrent disease. Eighteen patients (90%) remained disease free at the primary site, and the locoregional control rate is 80%. CONCLUSIONS: High-dose IA cisplatin and concurrent HFX-RT as used in this study is feasible and warrants further investigation. The high complete response rate and low grade 4 toxicity in this highly unfavorable subset of patients appears better than previously reported chemoradiation regimens for more favorable patients.

A multidimensional approach to breast cancer education.

BACKGROUND: This study was undertaken to present a multidimensional breast cancer education package (BCEP) to medical students in an effort to improve breast cancer education. METHODS: The students were exposed to a four-part BCEP consisting of a hands-on structured clinical instruction module (SCIM), a lecture, a problem-based learning (PBL) small-group discussion, and a written manual. Each component was evaluated with a questionnaire. Students responded to the items using a five-point Likert scale ranging from 1 (strongly disagree) to 5 (strongly agree). RESULTS: The mean overall evaluations for the BCEP components were: SCIM, 4.6; lecture, 4.0; manual 3.8, and PBL discussion, 3.6. Highly rated qualities of the SCIM included organization (4.7), faculty preparedness (4.8), and opportunity to practice skills (4.5). The students agreed that the lecture (4.1), manual (3.8), and PBL discussion (4.2) had prepared them for the SCIM. CONCLUSION: This innovative BCEP effectively improved students' understanding of breast cancer.

Preoperative chemoradiation in fixed distal rectal cancer: dose time factors for pathological complete response.

PURPOSE: Preoperative chemoradiation is being utilized extensively in the treatment of rectal cancer. However, a variety of dose time factors in both delivery of chemotherapy and irradiation remain to be established. This study was undertaken to examine the impact of dose time factors on pathological complete response (pCR) rates following preoperative chemoradiation for fixed rectal cancer. METHODS AND MATERIALS: Thirty-three patients with fixed rectal cancers were treated with combined 5-fluorouracil (5-FU) chemotherapy and pelvic radiation. Twenty-one patients received bolus 5-FU during the first 3-5 days of radiation and repeated on days 28-33 of their radiation treatment. Twelve patients were treated with continuous infusion (CI) 5-FU, 225 mg/m(2) for the duration of the pelvic radiation. Fifteen patients received a planned total radiation dose of 45 to 50 Gy and 18 patients received a dose of 55 to 60 Gy. Surgical resection was then carried out 6-8 weeks after completion of treatment. RESULTS: Diarrhea was the most frequent acute toxicity. Grade 3 diarrhea was observed in 6 patients requiring treatment interruption and was not related to the chemotherapy regimen. There was no Grade 4 or 5 toxicity. pCR was observed in 2 of 21 (10%) patients treated with bolus 5-FU as compared to 8 of 12 (67%) for patients treated with CI (p = 0.002). pCR were observed in 8 of 18 (44%) patients receiving radiation dose > or = 5500 cGy as compared to 2 of 15 (13%) patients treated to a dose < or = 5000 cGy (p = 0.05). In the high-dose radiation (> or = 5500 cGy) group, a significant difference in pCR rate was observed in patients treated with CI, 8 of 12 (67%) (p = 0.017) as compared with bolus 5-FU (0 of 6). There was no significant difference in operative morbidity or in wound healing between patients treated with bolus 5-FU or CI or within the groups treated with low or high doses of radiation. Three patients have developed local recurrence at 14 and 24 months, two in the low-dose group treated with bolus 5-FU and one patient in the CVI group. The overall 5-year survival for the whole group is 71%. CONCLUSION: Dose intensity of 5-FU and dose of radiation correlate significantly with the likelihood of achieving a pCR. Continuous infusion 5-FU (CI) and a preoperative radiation dose of 5500 cGy or higher can achieve pCR rates of approximately 50%, even in fixed cancers of the rectum.

Advances in the management of adrenal tumors.

Adrenal tumors are very common, with the majority being nonhypersecretory and benign and less than 1% being malignant. Most primary adrenal tumors are sporadic, but may be associated with other endocrine and familial disorders, especially pheochromocytoma. All patients with "sporadic" pheochromocytoma should be screened for MEN-2 and Von Hippel-Lindau disease. As in many endocrine tumors, there are no uniform definitive histologic criteria to distinguish malignancy, which is dependent on the clinical behavior of the tumor and is accurately diagnosed in the presence of adjacent organ invasion, recurrence, or distant metastasis. Surgery remains the cornerstone and the treatment of choice for functional and primary malignant adrenal tumors, both for cure and palliation, with low morbidity and mortality.

Stability and change in posttraumatic stress disorder symptoms following breast cancer treatment: a 1-year follow-up.

While some recent research has examined the prevalence and severity of posttraumatic stress disorder (PTSD)-like symptoms following cancer treatment, no research has examined temporal change or stability in these symptoms in cancer survivors. Female breast cancer survivors (n=46) participated in an initial telephone interview and a follow-up interview 12 months later. PTSD symptoms associated with breast cancer were assessed using the PTSD Checklist-Civilian version (PCLC). In general, PTSD symptoms in this population did not diminish over time. While group analyses indicated that PCLC-total and subscale scores were stable across the two assessments, analyses of PCLC scores indicated that many patients exhibited fairly large (>0.5 S.D.) increases and/or decreases in PCLC-total or subscale scores. Some evidence suggested that decreases in PCLC scores between the two study assessments were associated with greater social support and experience of fewer traumatic stressors prior to breast cancer diagnosis. Most significantly, the research suggested that women with greater PTSD symptoms at the initial interview were less likely to participate in the follow-up interview. Implications of this for research and clinical management of PTSD in this population are discussed.

Rheumatoid symptoms following breast cancer treatment: a controlled comparison.

The prevalence of rheumatoid symptoms following breast cancer (BC) treatment was examined. Breast cancer patients (n = 111) who were a mean of 27.6 months postcompletion of BC treatment and 99 otherwise healthy women with benign breast problems (BBP) completed a self-report measure that assessed current joint pain, swelling, and stiffness, as well as measures of quality of life. Results supported a hypothesized link between BC and rheumatoid symptoms: (1) the BC group was more likely to report joint stiffness lasting more than 60 min following morning waking; (2) the prevalence of unilateral or bilateral joint point or swelling was greater (P < 0.10) in the BC group for four of 10 joint-symptom combinations examined, with differences between the BC and BBP groups in upper extremity joint swelling particularly pronounced; and (3) 41% of the BC group reported that current rheumatoid symptoms exceeded those experienced prior to diagnosis. Within the BC group, the data did not support postchemotherapy rheumatism as an explanation for rheumatoid symptoms. Rather, data suggested that symptoms were associated with surgical management of BC. Finally, among women in the BC group with the most severe joint pain, only a minority were receiving medication for these symptoms. Given the relationship between rheumatoid symptoms and quality of life, more systematic research examining potential contributing factors such as menopausal status, concurrent lymphedema, and weight gain is warranted.

Postoperative radiation therapy for primary vs. recurrent squamous cell carcinoma of the head and neck: results of a comparative analysis.

BACKGROUND: There is little literature comparatively evaluating the results of postoperative radiation therapy (RT) for patients with squamous cell carcinoma (SCC) of the head and neck treated for primary versus recurrent disease. METHODS: Between 1981 and 1993, 174 patients with SCC of the head and neck, 143 with primary and 31 with recurrent disease, were treated with standard postoperative RT. RESULTS: Patients treated for primary disease had 5-year local-regional control (LRC) and disease-specific survival (DSS) rates of 69% and 54%, respectively, as compared with 46% and 32%, respectively, for patients treated for recurrent disease (P = 0.03 and 0.04, respectively). On multivariate analysis, only tumor type (primary vs recurrent) significantly influenced LRC (P = 0.003) and only primary tumor site (oral cavity vs nonoral cavity) significantly influenced DSS (P = 0.04). Among the patients treated for recurrent disease, site of recurrence (undissected vs dissected tissue) significantly influenced both LRC and DSS (P = 0.008 and 0. 001, respectively). CONCLUSIONS: Patients with recurrent SCC of the head and neck do poorly as compared with those with primary disease when treated with standard postoperative RT, particularly when the recurrence is within previously dissected tissue. This patient group should be targeted for alternative treatment strategies.

Risk factors for pain after mastectomy/lumpectomy.

PURPOSE: Careful study of risk factors that predispose an individual to developing postmastectomy pain (PMP) after breast cancer surgery has not been reported. This study examined potential risk factors for PMP including demographic, disease, and treatment variables, as well as surgical factors, such as surgical technique and number of lymph nodes removed. DESCRIPTION OF THE STUDY: Data were collected via telephone interviews and review of medical records. Pain was assessed using the Brief Pain Inventory. The sample included 134 breast cancer survivors who were a mean age of 55 years (SD = 9) and a mean of 35 months postsurgery (SD = 19). RESULTS: Women with PMP (n = 36) were not significantly different from women without PMP (n = 98) on demographic, disease, treatment, or surgical variables. PMP intensity was not significantly associated with age at diagnosis, time postsurgery, or time post-treatment. Contrary to expectation, PMP was found in women postlumpectomy without axillary dissection, women whose intercostobrachial nerve was spared, and women without documented postoperative complications. CLINICAL IMPLICATIONS: Findings suggest that cases of PMP cannot uniformly be identified based on the presence or absence of certain factors. Findings also underscore the need to screen all women for PMP after breast cancer surgery, particularly given the availability of effective pain management therapies.

Advances in the pathogenesis and treatment of thyroid cancer.

Thyroidectomy remains the mainstay of treatment for thyroid carcinoma. The extent of surgical resection, however, remains controversial as most patients will have excellent long-term prognosis and because some of the standard staging and prognostic information are not available at the time of surgical resection. The different staging and risk group definitions for thyroid carcinoma are not superior to the Tumor-Node-Metastasis classification of the American Joint Commission in Cancer (AJCC), which is universally available and accepted and should be used to report treatment outcomes. Recent advances in the molecular pathogenesis of thyroid malignancy will help identify high-risk patients who would benefit from aggressive surgical resection and adjuvant treatment.

Hypertension in patients with pheochromocytoma.

Adrenal-dependent hypertension syndromes are uncommon forms of hypertension. They include primary aldosteronism, pheochromocytoma, Cushing"s syndrome, and congenital adrenal hyperplasia. Pheochromocytomas are the cause of hypertension in 0.1% to 0.2% of hypertensive patients. Excess catecholamine release and other neural and humoral mechanisms contribute to the pathophysiology of hypertension. Patients with pheochromocytomas have a potentially curable cause of endocrine hypertension and, if undetected, pheochromocytomas confer a high risk for morbidity and mortality, especially during surgical procedures and pregnancy. All patients with incidental adrenal tumors, regardless of tumor size, should be biochemically screened for pheochromocytoma (especially before resection or needle biopsy) to avoid precipitation of a lethal hypertensive crisis.

Bilateral radial forearm free flaps for oral-cavity reconstruction.

Simultaneous primary tumors (tumors found at the same time or within 1 month of each other) are not uncommon in head and neck cancer. Most frequently, one lesion is small relative to the other; however, this is not always the case When two anatomically separate simultaneous primary tumors are large, a challenge for the reconstructive surgeon exists. The authors present a case of simultaneous primary tumors arising along the left and right mandibular gingiva. Following extirpation of the tumors, the defects were reconstructed with bilateral free radial forearm flaps. They conclude that this procedure is an excellent option for reconstruction of anatomically separate simultaneous defects of the head and neck region. This reconstruction provides an excellent tissue match for the intraoral region, and can be accomplished with minimal morbidity in a relatively short operative time.

Physical symptoms, distress, and breast cancer risk perceptions in women with benign breast problems.

Physical symptoms, general and breast cancer-specific distress, and perceived breast cancer risk were assessed in 66 women with benign breast problems (BBP) and 66 age-matched healthy comparison (HC) women. BBP women reported significantly greater worry about breast cancer than HC women. Breast symptom incidence and breast cancer risk perceptions were found to mediate group differences in breast cancer worry. Hierarchical regression analyses indicated that perceptions of control over a potential breast cancer prognosis moderate the impact of breast symptoms on reports of breast cancer worry. Implications for risk counseling with BBP women are discussed.

Hot flashes in postmenopausal women treated for breast carcinoma: prevalence, severity, correlates, management, and relation to quality of life.

BACKGROUND: Research on hot flashes (HFs) after the diagnosis and treatment of breast carcinoma (BC) is scarce. To our knowledge, this research represents the second study of HF prevalence and severity in women with BC and the first study of 1) correlates of HF prevalence and severity, 2) use of HF management strategies, and 3) the relation between HFs and quality of life (QOL) among women with BC. METHODS: Eligible women (n = 136) participated in structured telephone interviews. RESULTS: Of the 114 postmenopausal women interviewed, 65% reported HFs, with 59% of women with HFs (n = 74) rating the symptom as severe. Multivariate analysis revealed that 1) HFs were most common in women with a high school education or less and those who were younger at diagnosis and 2) HFs were most severe in women with a higher body mass index, those who were younger at diagnosis, and those receiving tamoxifen. Among women with HFs, 37% were not using any HF management strategies and 63% expressed interest in learning more regarding > or = 1 strategy. HFs marginally were related to decreased mental and physical QOL using the SF-12 Health Survey (P < 0.10). CONCLUSIONS: The results of the current study significantly contribute to knowledge regarding HFs in women with BC and support the need for carefully controlled clinical trials evaluating interventions for relieving HFs in this population.

Thyroid lymphoma: is there a role for surgery?

The role of surgery in the treatment of Stage I and II non-Hodgkin's thyroid lymphoma (NHTL) is not well defined. At our institution, we have treated seven patients (six women and one man) with NHTL during the past 6 years. Three patients (43%) had a prior history of thyroid disease, usually lymphocytic thyroiditis. Clinical symptoms included a rapidly enlarging neck mass (86%), dysphagia (71%), dyspnea (71%), and hoarseness (71%). Five patients (71%) had hypothyroidism; one patient, hyperthyroidism; and one patient, normal thyroid function. Five patients underwent fine-needle aspiration (FNA) at our institution. In three instances, FNA results were indicative of NHTL; the remaining FNA tests yielded no diagnosis. Surgical procedures were varied: incisional biopsy (n = 4), limited tumor debulking with tracheostomy (n = 2), and thyroidectomy (n = 1). Each of the seven patients was found to have large cell lymphoma. Treatment consisted of combination chemotherapy with consolidative irradiation. All tumors dramatically decreased in size soon after the initiation of therapy. One patient refused radiotherapy. All patients except one are still alive (median follow-up, 24 months). In conclusion, 1) a diagnosis of NHTL, although rare, should be considered when patients have rapidly growing goiters; 2) FNA is a useful first step in diagnosing NHTL; 3) NHTL is exquisitely sensitive to both chemotherapy and radiation; 4) surgical intervention is generally confined to incisional biopsy with occasional limited pretracheal tumor debulking; and 5) when a biopsy is obtained from a patient suspected of having NHTL, immediate processing by the pathologist is recommended so that material can be obtained for special studies as needed.

Critical assessment of the head and neck clinical skills of general surgery residents.

Head and neck surgery is an important part of general surgery. There is, however, little information about the quality of residents' clinical skills in this important field. In an Objective Structured Clinical Examination (OSCE), residents encounter multiple patients with various clinical problems and are rated by faculty members using objective criteria. This study was undertaken to assess the head and neck surgery skills of a group of general surgical residents. Fifty-one general surgery residents examined the same nine patients with head and neck disease. Faculty members graded each clinical interaction according to preset objective criteria. Both actual (e.g., thyroid nodule, oral cancer follow-up examination) and simulated (e.g., dysphagia) patients were used in the OSCE. The reliability of the examination was assessed by coefficient alpha. The construct validity was determined by a two-way analysis of variance with one repeated measure. The reliability was 0.75 for the clinical examination. Performance varied by level of training: Residents performed at a higher level than interns (p < 0.0001), but overall scores were poor (mean score 55%). Important deficits in skills were identified at all levels of training. It is concluded that more attention should be focused on specific outcome assessments of surgical training programs and on strategies for upgrading the clinical skills of surgical residents.

Advances in the diagnosis and therapy of adrenal tumors.

There continues to be controversy regarding the optimal evaluation and treatment of adrenal tumors. Magnetic resonance imaging, metaiodobenzylguanidine scan, single-photon emission tomography imaging, endoscopic ultrasound, and radiolabeled somatostatin analogues are just a few of the newer imaging techniques being investigated to improve our ability to obtain a specific diagnosis of an adrenal mass. Although the diagnosis and treatment of pheochromocytomas are relatively straightforward, the evaluation and treatment of incidentally discovered adrenal masses is less clear-cut. The management of an incidentaloma is guided by two principle considerations: whether the tumor has hormonal activity, and its malignant potential. In addition to diagnostic advances, refinements continue to be made regarding surgical management of these lesions. Laparoscopic adrenalectomy is fast becoming the procedure of choice for benign-appearing adrenal masses with appropriate indications for operative removal.

Postmastectomy/postlumpectomy pain in breast cancer survivors.

Few studies have focused on careful assessment of postmastectomy pain (PMP); a chronic neuropathic pain syndrome that can affect women postlumpectomy or postmastectomy for breast cancer (BC). Study aims were to determine the prevalence of PMP in an outpatient sample of breast cancer survivors (BCS), describe subjective and objective characteristics of PMP, and examine the relationship between PMP and quality of life. Breast cancer survivors (n = 134) participated in telephone interviews, and those reporting PMP (n = 36) were invited to a pain center for further evaluation and treatment. Results show PMP is a distinct, chronic, pain syndrome affecting 27% of BCS. Findings support the need for clinical trials evaluating the effectiveness of nonpharmacological or cognitive behavioral therapies in alleviating mild to moderate PMP.