Outcome of patients with transformed indolent non-Hodgkin lymphoma referred for autologous stem-cell transplantation.

BACKGROUND: The proportion of potentially eligible patients with transformed indolent non-Hodgkin lymphoma who undergo autologous stem-cell transplantation (ASCT) is unknown. There are limited data describing their outcome in the rituximab era. PATIENTS AND METHODS: We reviewed 105 consecutive patients with biopsy-proven transformation referred to Princess Margaret Hospital for consideration of ASCT during 1996-2009. Patients received anthracycline or platinum-based chemotherapy with or without rituximab. Responders proceeded to stem-cell mobilization and ASCT. RESULTS: The median age at transformation was 54 (range 30-65) years. Patients received a median of two chemotherapy regimens for transformation, including rituximab in 39%. Fifty patients (48%) proceeded with ASCT and 55 (52%) did not, mainly due to progressive disease (n = 42). Three-year overall (OS) and progression-free survival (PFS) post-ASCT were 54% and 42%, respectively. Patients receiving rituximab with chemotherapy before transplant had a 3-year post-ASCT OS of 71% versus 47% in those who received chemotherapy alone (P = 0.046). Patients transplanted after 2004 had a 3-year post-ASCT OS of 69% versus 39% in those receiving ASCT earlier (P = 0.009). CONCLUSIONS: About half of transplant-eligible patients with transformation are able to undergo ASCT. Outcomes following ASCT appear to have improved over recent years, although the role of rituximab in this patient population requires further evaluation.

Predictive factors for persistent and late radiation complications in breast cancer survivors.

PURPOSE: With improved diagnostic techniques and treatments of breast cancer, overall survival times are longer, giving more opportunity for normal tissue complications of treatment to manifest. Radiation late effects (RLEs) could have profound long-term impacts on the quality of life of the survivors. The aim of this study was to identify predictive factors influencing timing and types of complications in patients referred to the Adult Radiation Late Effects Clinic (ARLEC). METHODS: In a period of 16 years, 296 breast cancer patients were referred to the ARLEC. The clinical records were retrospectively studied to collect epidemiologic, medical and treatment data. Associations were sought between candidate predictive factors and time to the first complication after radiation treatment (RT) completion (primary outcome), and pain or swelling (secondary outcomes) using univariable and multivariable linear and logistic regression analyses. All analyses were performed in SAS, version 9.4. RESULTS: All patients were female with a mean age of 56.3 years. The first treatment-related complication occurred after a median of 3 months. Patients were followed at ARLEC for a median of 18 months. Older age and delay from surgery to RT (S-RT delay) were associated with earlier onset of complications (both p < 0.001). The most common complications were breast pain (62.1%) and swelling (45.9%). Histology and RT boost were associated with pain (p = 0.035 and 0.013). RT boost and S-RT delay on the other hand were associated with swelling (p = 0.013 and 0.005). CONCLUSIONS: Clinical factors identified could help recognize the patients at high risk for developing RLEs and alert physicians to initiate earlier diagnostic and therapeutic measures.

Personalizing post-treatment cancer care: a cross-sectional survey of the needs and preferences of well survivors of breast cancer.

Background: Improved treatments resulting in a rising number of survivors of breast cancer (bca) calls for optimization of current specialist-based follow-up care. In the present study, we evaluated well survivors of bca with respect to their supportive care needs and attitudes toward follow-up with various care providers, in varying settings, or mediated by technology (for example, videoconference or e-mail). Methods: A cross-sectional paper survey of well survivors of early-stage pT1-2N0 bca undergoing posttreatment follow-up was completed. Descriptive and univariable logistic regression analyses were performed to examine associations between survivor characteristics, supportive care needs, and perceived satisfaction with follow-up options. Qualitative responses were analyzed using conventional content analysis. Results: The 190 well survivors of bca who participated (79% response rate) had an average age of 63 ± 10 years. Median time since first follow-up was 21 months. Most had high perceived satisfaction with in-person specialist care (96%, 177 of 185). The second most accepted model was shared care involving specialist and primary care provider follow-up (54%, 102 of 190). Other models received less than 50% perceived satisfaction. Factors associated with higher perceived satisfaction with non-specialist care or virtual follow-up by a specialist included less formal education (p < 0.01) and more met supportive care needs (p < 0.05). Concerns with virtual follow-up included the perceived impersonal nature of virtual care, potential for inadequate care, and confidentiality. Conclusions: Well survivors of bca want specialists involved in their follow-up care. Compared with virtual follow-up, in-person follow-up is perceived as more reassuring. Certain survivor characteristics (for example, met supportive care needs) might signal survivor readiness for virtual or non-specialist follow-up. Future work should examine multi-stakeholder perspectives about barriers to and facilitators of shared multimodal follow-up care.

Afatinib in advanced pretreated non-small-cell lung cancer- a Canadian experience.

Background: Afatinib, an irreversible epidermal growth factor receptor tyrosine kinase inhibitor (egfr tki), is approved for first-line therapy in advanced EGFR mutation-positive non-small-cell lung cancer (nsclc) and has previously demonstrated activity after failure of chemotherapy and reversible egfr tkis, with improved response and progression-free survival, compared with placebo. Outcomes in pretreated patients with advanced nsclc receiving afatinib through a Canadian special access program (sap) are reported here. Methods: Patients with nsclc progressing after at least 1 line of chemotherapy and an egfr tki were eligible to enrol in the sap. Characteristics of patients from the two largest accruing Canadian centres were retrospectively reviewed, including demographics, disease and treatment data, and patient outcomes. Results: The 53 patients who received afatinib (57% women, 51% never-smokers, 26% of East Asian ethnicity, and 66% with adenocarcinoma) had a median age of 59 years. EGFR mutations were documented in 25%, and EGFR wild-type in 8%. All patients had received prior egfr tki treatment, with 42% achieving a response. Patients took afatinib for a median of 2 months (range: 0-26 months); 17% required 1 or more dose reductions. Of 47 evaluable patients receiving afatinib, 10 experienced tumour shrinkage, and 11, stable disease. Median survival from afatinib initiation was 5 months (95% confidence interval: 2 months to 8 months). Grade 3 or greater diarrhea, rash, paronychia, and stomatitis were seen in 9%, 11%, 6%, and 4% of patients respectively. Conclusions: In an unselected population of pretreated patients with advanced nsclc after tki failure, median survival with afatinib therapy was 5 months. Through a sap, afatinib demonstrated activity in clinical practice, with manageable toxicity.

Outcomes in Patients Treated with Post-mastectomy Chest Wall Radiotherapy without the Routine Use of Bolus.

AIMS: The use of bolus in post-mastectomy radiotherapy (PMRT) varies significantly between institutions. We report on chest wall recurrence and acute toxicity rates for PMRT patients treated with selective use of bolus. MATERIALS AND METHODS: We analysed PMRT patients who received adjuvant chest wall radiotherapy for invasive breast cancer between 2004 and 2009. Patient, tumour and cancer outcomes were collected from a prospective database, with additional radiotherapy and acute toxicity details supplemented retrospectively. Chest wall bolus was reserved for patients considered at high risk of local recurrence. RESULTS: There were 314 patients suitable for analysis: 52 received bolus, 262 did not. The mean age was 53.2 years. The median follow-up was 4.2 years. The most common T stage was T2 (37%), followed by T3/T4 (33%). There were 229 patients (73%) who had N+ disease; 213 (68%) patients had grade 3 cancer. Oestrogen receptor was positive in 176 (56%) cases, progesterone receptor was positive in 134 (43%) and HER2 receptor was positive in 24 (8%). Lymphovascular space invasion was present in 146 patients (46%), dermal invasion in 30 patients (10%) and positive margin in 14 patients (4%). The 4 year chest wall recurrence rate was 14% (95% confidence interval 5.4-26.8%) in the bolus group and only 3.5% (95% confidence interval 1.6-6.4%) in the non-bolus group. On univariate analysis, use of bolus was associated with a significant difference in chest wall recurrence (hazard ratio 3.09; 1.15-8.33; P = 0.025). However, when taking into account margin status, this significance was lost (hazard ratio = 2.45; 95% confidence interval 0.80-7.50, P = 0.12). There was a higher rate of acute grade 2 skin toxicity in patients receiving bolus compared with those without, 40% versus 21% (P = 0.01). CONCLUSIONS: The selective use of bolus resulted in a small risk of chest wall recurrence rates for low-risk patients. This suggests that the routine use of bolus in PMRT patients may be unnecessary.

Treatment of metastatic prostatic cancer with low-dose prednisone: evaluation of pain and quality of life as pragmatic indices of response.

Thirty-seven men with symptomatic bone metastases from prostate cancer that had progressed following earlier treatment with estrogens and/or orchidectomy were treated with low-dose prednisone (7.5 to 10 mg daily). The rationale for this treatment was that some patients might still have hormone-sensitive disease that was stimulated by weak androgens of adrenal origin, and that these androgens could be suppressed by prednisone through its negative feedback on secretion of adrenocorticotrophic hormone (ACTH). Response to treatment was assessed by requirement for analgesics, by the McGill-Melzack pain questionnaire, and by a series of 17 linear analog self-assessment (LASA) scales relating to pain and to various aspects of quality of life. Fourteen patients (38%) had improvement in indices used to assess pain at 1 month after starting prednisone, and seven patients (19%) maintained this improvement for 3 to 30 months (median, 4 months). Reduction in pain was associated with improvement in other dimensions of quality of life, and in the scale for overall well-being. Prednisone treatment led to a decrease in the concentration of serum testosterone in seven of nine patients where it was not initially suppressed below 2 nmol/L, and caused a decrease in serum levels of androstenedione and dehydroepiandrosterone sulfate in more than 50% of patients. Symptomatic response was associated with a decrease in serum concentration of adrenal androgens. We conclude that (1) low-dose prednisone may cause useful relief of pain in some patients with advanced prostatic cancer; (2) relief of pain was associated with suppression of adrenal androgens; and (3) measures of pain and quality of life can be used to assess possible benefits of systemic therapy in patients with metastatic prostate cancer.

Sequential chemotherapy and radiation for nasopharyngeal cancer: absence of long-term benefit despite a high rate of tumor response to chemotherapy.

Between April 1981 and December 1983, patients with locoregional carcinoma of the nasopharynx were treated with two courses of chemotherapy administered before radiation therapy. Chemotherapy consisted of methotrexate, bleomycin, and cisplatin, which were administered at 3-week intervals, and radiation therapy was scheduled to commence 3 weeks after the start of the second course. Forty-nine of 51 consecutive patients were treated; only one patient progressed on chemotherapy, and of 36 patients with measurable neck nodes, eight had complete and 19 had partial clearance (greater than 50% decrease in cross-sectional area) of these nodes when assessed before initiation of radiotherapy. Despite the high rate of tumor response (75%; 95% confidence limits, 59% to 91%), the actuarial survival and disease-free survival curves were almost identical to those recorded for a consecutive group of 140 historical controls of similar stage distribution treated with radiation alone. This chemotherapy provided a high rate of tumor remission, but did not appear to convey long-term benefit to patients when used before radiation therapy.

Maternal and fetal outcome after invasive cervical cancer in pregnancy.

Invasive carcinoma of the cervix is the most common gynecologic malignancy to occur during the reproductive years. To analyze the effects of pregnancy on the course and survival of invasive cervical cancer, we compared 40 women with invasive cervical cancer to 89 nonpregnant controls matched for age, calendric year of diagnosis, stage, and tumor type. Additionally, we compared the distribution of invasive cervical cancer stages among the 40 pregnant women with that among the 1,963 cases of invasive cervical cancer treated during the same 30 years in women less than 45 years of age registered in the same hospital. To evaluate pregnancy outcome, we compared babies born to women with invasive cervical cancer to babies born of women matched for maternal age and not exposed to known teratogens or reproductive risks during pregnancy. Thirty-year survival of pregnant women with invasive cervical cancer was identical to that of their matched controls. Women having invasive cervical cancer were 3.1 times more likely to be diagnosed with stage I disease (95% confidence interval, 1.6 to 6.2). Additionally, they had a significantly lower chance of being diagnosed with stages III and IV (P = .02). Babies born to women with invasive cervical cancer were similar in gestational age and rates of prematurity but had a lower birth weight than the matched controls. There were two stillbirths among the 24 pregnancies that continued to term (8%), not statistically different from the 1.1% rate for Ontario. Our data suggest that pregnancy per se does not adversely affect the survival of women with invasive cervical cancer. However, this study provides evidence that pregnant women are more likely to present with early disease because of regular, pregnancy-related obstetric exams. Moreover, there is an increased risk for stillbirth, which should lead to follow-up of these patients by a high-risk perinatal unit.

Management of stage II seminoma.

PURPOSE: To assess the results of treatment, patterns of failure, and prognostic factors for relapse in a contemporary cohort of patients with stage II seminoma. MATERIALS AND METHODS: From January 1981 and December 1993, 99 patients (median age, 35 years) with stage II seminoma (IIA, 41; IIB, 28; IIC, 24; IID, six) were managed at our institution. Eighty were treated with radiation therapy (RT) and 19 with chemotherapy (ChT). RESULTS: With a median follow-up of 6.7 years, the five-year overall actuarial survival was 94%, the 5-year cause-specific survival was 94%, and the 5-year relapse-free rate was 83%. Sixteen (20%) of the 80 patients treated with RT relapsed (median time to relapse, 9 months). Relapse occurred outside the irradiated area in all but two patients. Distant relapse sites included the supraclavicular fossa, bone (four patients, three with spinal cord compression), and lung/mediastinum. All 19 patients treated primarily with ChT achieved disease control and none has relapsed. The relapse rate at 5 years for patients with stage IIA to IIB was 11% (seven of 64), and 56% (nine of 16) for those with stage IIC to IID disease (P < .0001). No patient with IIC or IID disease treated with ChT relapsed as compared with 56% of patients treated with RT (0 of 14 v nine of 16, P = .002). CONCLUSION: Radiation therapy is highly effective in patients with stage IIA or IIB seminoma (89% were relapse free). In stage IIC or IID disease, although local control with RT is excellent, a 50% risk of distant relapse is unacceptable, and not all patients who relapse can be salvaged. Chemotherapy should clearly be the primary treatment in patients with stage IIC or IID seminoma.

Stage I testicular seminoma: results of adjuvant irradiation and surveillance.

PURPOSE: To assess the results of treatment and patterns of relapse in a contemporary group of patients with stage I testicular seminoma managed by adjuvant radiation therapy (RT) and surveillance. PATIENTS AND METHODS: Between January 1981 and December 1991, 364 patients with stage I seminoma were treated at Princess Margaret Hospital. Of these, 194 were treated with adjuvant RT (92% received a dose of 25 Gy in 20 fractions for 4 weeks) and 172 were managed by surveillance. Two patients were included in this series twice--both had postorchiectomy RT for stage I disease, developed a contralateral seminoma, and were placed on surveillance and analyzed for outcome of both primary tumors. The median follow-up period for patients treated with adjuvant RT was 8.1 years (range, 0.2 to 12), and for patients managed by surveillance, it was 4.2 years (range, 0.6 to 10.1). RESULTS: The overall 5-year actuarial survival rate for all patients was 97%, and the cause-specific survival rate was 99.7%. Only one patient died of seminoma. Of 194 patients treated with RT, 11 have relapsed, with a 5-year relapse-free rate of 94.5%. Prognostic factors for relapse included histology, tunica invasion, spermatic cord involvement, and epididymal involvement. Twenty-seven patients developed disease progression on surveillance, which resulted in a 5-year progression-free rate of 81.9%. The only factor identified to predict progression on surveillance was age at diagnosis: patients aged < or = 34 years had a 26% risk of progression at 5 years, in contrast to a 10% risk of progression in those greater than 34 years of age. CONCLUSION: The outcome of patients with stage I testicular seminoma is excellent, with only one of 364 patients (0.27%) dying of disease. In our experience, both a policy of adjuvant RT and of surveillance resulted in a high probability of cure. Our surveillance experience showed that four of five patients with stage I seminoma are cured with orchiectomy alone. The benefit of adjuvant RT was reflected in a decreased relapse rate. We have identified a number of prognostic factors for relapse in patients managed with both approaches, but further study of prognostic factors is required, particularly to identify patients at high risk of disease progression on surveillance.

Economic evaluation of chemotherapy with mitoxantrone plus prednisone for symptomatic hormone-resistant prostate cancer: based on a Canadian randomized trial with palliative end points.

PURPOSE: To evaluate the economic consequences of the use of chemotherapy in patients with symptomatic hormone-resistant prostate cancer (HRPC) in the context of a previously published Canadian open-label, phase III, randomized trial with palliative end points. PATIENTS AND METHODS: The trial randomized 161 patients to initial treatment with mitoxantrone and prednisone (M + P) or to prednisone alone (P) and showed better palliation with M + P. There was no significant difference in survival. A detailed retrospective chart review was performed of resources used from randomization until death of 114 of 161 patients enrolled at the three largest centers: these included hospital admissions, outpatient visits, investigations, therapies (which included all chemotherapy and radiation), and palliative care. Cancer center and community hospital costs were calculated by using the hotel approximation method and case costing from the Ontario Case Cost Project, respectively. Cost-utility analysis was performed by transforming the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 global quality-of-life item measured every 3 weeks on trial to an estimate of utility, and extending the last known value through to death or last follow-up. RESULTS: The mean total cost until death or last follow-up by intention-to-treat was M + P CDN $27,300; P CDN $29,000. The 95% confidence intervals on the observed cost difference ranged from a saving of $9,200 for M + P (with palliative benefit) to an increased cost of $5,800 for M + P. The major proportion of cost (M + P 53% v P 66%; CDN $14,500 v $19,100) was for inpatient care. Initial M + P was consistently less expensive in whichever time period was used to compare costs. Cost-utility analysis showed M + P to be the preferred strategy with an upper 95% confidence interval for the incremental cost-utility ratio of CDN $19,700 per quality-adjusted life-year (QALY). CONCLUSION: A treatment that reduces symptoms and improves quality of life has the potential to reduce costs in other areas. Economic factors should not influence the clinical decision as to whether to use M + P in a symptomatic patient.

Fetal outcome after in utero exposure to cancer chemotherapy.

BACKGROUND: Cancer is the second leading cause of death of women during the reproductive years, and its occurrence in pregnancy is between 0.07% and 0.1%. METHODS: To analyze the effect of cancer on pregnancy, we compared 21 pregnancies occurring during 30 years in women who received chemotherapy for their cancer with a control group matched for maternal age and composed of women not exposed to known teratogens or reproductive risks during pregnancy. RESULTS: Of 13 women exposed to chemotherapy during the first trimester, two of five whose pregnancies continued to term had major malformations in their infants, four had spontaneous abortions, and four had therapeutic abortions. Of four women with second-trimester exposure to chemotherapy, two had normal live births, one had a stillbirth, and one had a therapeutic abortion. All four pregnancies exposed to chemotherapy during the third trimester resulted in healthy live births. Infants exposed to chemotherapy had statistically significantly lower birth weights than their matched controls (2227 +/- 558 g vs 3519 +/- 272 g, P less than .001), due to both significantly lower gestational age and substantial intrauterine growth retardation (P less than .01). The trend for higher rate of stillbirth (1/11) agrees well with 10 stillbirths among all women with cancer in pregnancy without and with chemotherapy who gave birth (n = 223), when compared with the population of Ontario (P less than .0005). CONCLUSIONS: This study confirms the increased likelihood of spontaneous abortions and major birth defects when chemotherapy is used during embryogenesis, whereas such a risk is not apparent beyond the first trimester. Because of the higher risk of stillbirth and intrauterine growth retardation, women with cancer should be monitored closely by a high-risk obstetric unit to define the optimal time of delivery.

The prognostic significance of the tumour infiltrating lymphocyte count in stage I testicular seminoma managed by surveillance.

The degree of lymphocytic infiltration is a significant determinant of outcome for a variety of malignancies, but its role in seminoma is unknown. 150 men with stage I testicular seminoma presenting between 1981 and 1993 were managed by surveillance following orchidectomy. The presence of tumour infiltrating lymphocytes (TILs) in each case was classified as high, intermediate or low. At a median follow-up of 9.4 years, 30 of the 150 men developed recurrent seminoma. On univariate analysis, the risk of relapse was associated with age < or =33 years (P=0.002), tumour diameter >6 cm (P=0.03), lymphatic or vascular invasion (P=0.04), tumour invasion of rete testis (P=0.05), and lower TIL count (P=0.02). On multivariate analysis, statistically significant predictors of risk of relapse were age < or =33 years (hazard ratio (HR) 4.6 (95% confidence intervals (CI): 1.7-12.2)) and tumour diameter >6 cm (HR 2.8 (CI: 1.2-6.5)). Lower TIL count was of borderline statistical significance (HR 1.8 (CI: 0.96-3.44)). The functional role of the lymphocytic infiltrate in testicular seminoma warrants further study.

Symptom response after palliative radiotherapy for patients with brain metastases.

Whole brain radiotherapy (RT) is frequently used to palliate symptoms in patients with brain metastases, but the palliative benefit to patients has not been well documented. We conducted a longitudinal observational prospective study of patients receiving standard RT (20 Gray (Gy)/5 fractions) for symptomatic brain metastases. End-points were observer rating of neurological symptoms, patient-rated symptoms, performance status, neurological functional status, cognitive function and quality of life (QOL). Median survival for the 75 patients was 86 days (95% confidence interval (CI): 65-101 days). At 1 month, 19% of patients showed an improvement or resolution of presenting symptoms, 23% were stable and 55% had progressed or died. Patient-rated symptoms were increased at 1 month in comparison to baseline data. Only 4 patients had an improved performance status and 22 were stable. Many patients with brain metastases have a short life expectancy and may not benefit from even short duration radiation schedules. Further effort is needed to optimise patient selection and tailor treatment appropriately.

Papillary and follicular thyroid cancer. Prognostic factors in 1,578 patients.

This report from the Canadian survey of thyroid cancer describes 1,074 patients with papillary thyroid cancer and 504 with follicular thyroid cancer followed for four to 24 years. The study groups included more patients with "advanced" disease and fewer with "early" disease than in the general population because these patients were referred to radiotherapy cancer centers, sometimes routinely, but often because referring physicians believed that certain clinical features indicated the need for additional treatment. Although this report is subject to all the problems of retrospective studies, a careful assessment of the pretreatment extent of disease combined with a long follow-up period has allowed an analysis of prognostic factors with considerable confidence. Univariate analysis of 12 possible prognostic factors (excluding treatment) demonstrated that nine of them were of statistical significance: postoperative status, age at diagnosis, extrathyroidal invasion, distant metastases, nodal involvement, differentiation, sex, tumor size, and pathologic type (in descending order of importance). Multivariate analysis was carried out using cause-specific survival rates. Independently important prognostic factors at initial treatment were age at diagnosis, extrathyroidal invasion, and degree of differentiation histologically for papillary cancers; and extrathyroidal invasion, distant metastases, primary tumor size, nodal involvement, age at diagnosis, and postoperative status for follicular cancers. The prognostic factors for tumor recurrence were quite different for the papillary and follicular cancers and ranked differently for the two groups.

Analysis of cause-specific failure endpoints using simple proportions: an example from a randomized controlled clinical trial in early breast cancer.

PURPOSE: To describe a statistically valid method for analyzing cause-specific failure data based on simple proportions, that is easy to understand and apply, and outline under what conditions its implementation is well-suited. METHODS AND MATERIALS: In the comparison of treatment groups, time to first failure (in any site) was analyzed first, followed by an analysis of the pattern of first failure, preferably at the latest complete follow-up time common to each group. RESULTS: A retrospective analysis of time to contralateral breast cancer in 777 early breast cancer patients was undertaken. Patients previously treated by mastectomy plus radiation therapy to the chest wall and regional nodal areas were randomized to receive further radiation and prednisone (R+P), radiation alone (R), or no further treatment (NT). Those randomized to R+P had a statistically significantly delayed time to first failure compared to the group randomized to NT (p = 0.0008). Patients randomized to R also experienced a delayed time to first failure compared to NT, but the difference was not statistically significant (p = 0.14). At 14 years from the date of surgery (the latest common complete follow-up time) the distribution of first failures was statistically significantly different between R+P and NT (p = 0.005), but not between R and NT (p = 0.09). The contralateral breast cancer first failure rate at 14 years from surgery was 7.2% for NT, 4.6% for R, and 3.7% for R+P. The corresponding Kaplan-Meier estimates were 13.2%, 8.2%, and 5.4%, respectively. CONCLUSION: Analyzing cause-specific failure data using methods developed for survival endpoints is problematic. We encourage the use of the two-step analysis strategy described when, as in the example presented, competing causes of failure are not likely to be statistically independent, and when a treatment comparison at a single time-point is clinically relevant and feasible; that is, all patients have complete follow-up to this point.

Enhanced control by radiotherapy of cervical lymph node metastases arising from nasopharyngeal carcinoma compared with nodal metastases from other head and neck squamous cell carcinomas.

PURPOSE: To test the hypothesis that metastatic cervical lymph nodes arising from nasopharyngeal carcinoma (NPC) are more readily controlled with radiotherapy than comparable nodes from squamous cell carcinomas of other head and neck sites (SCC). METHODS AND MATERIALS: One hundred four NPC patients with metastatic cervical nodes (mean size of the largest node equals 4.1 cm) were randomly selected from radiation treatment files for two time periods, 1969-1976 and 1983-1988, when radiation alone was the first line treatment. Candidate controls were selected randomly from radiation treatment files of node positive squamous cell carcinomas arising from the oropharynx, hypopharynx, oral cavity or larynx who were also treated by radical radiation therapy as sole initial treatment in the 1970s and 1980s. Each NPC case was matched with a control using the size of the largest involved node as the matching criterion. The median follow-up of all 208 patients was 3 years (4.2 years in NPC cases and 1.4 years in the matched controls). For those who were alive at last follow-up, the median follow-up for both arms was 7.7 years (6.7 years in NPC cases and 10.2 years in the matched controls). Nodal control was evaluated by clinical neck examination in both arms. Nodal recurrence was defined as relapse or persistence of metastatic nodal disease from day 1 of radiotherapy treatment. RESULTS: Despite a similar mean delivered dose to involved neck nodes (52.9 Gy for the NPC group and 53.9 Gy for the matched controls), the SCC group had significantly worse nodal control with radiation when compared to the NPC group (p < 0.0001, relative risk 3.0, 95% [1.8, 5.1]). The 3-year nodal recurrence-free rate among NPC cases was 71 +/- 5%, compared to 43 +/- 5% among matched controls. CONCLUSION: The result of this study supports the hypothesis that metastatic cervical nodes from NPC are more readily controlled by irradiation than cervical nodes of similar size arising from other head and neck squamous cell carcinomas. Further study is required to explore the reasons for this apparent radiosensitivity.

An analysis of 78 breast sarcoma patients without distant metastases at presentation.

PURPOSE: A retrospective review of a single cancer center experience was undertaken to identify clinical or treatment prognostic factors for these unusual tumors, to allow for a recommendation regarding management. METHODS AND MATERIALS: The charts of 76 women and 2 men with breast sarcoma and without distant metastases at presentation registered from 1958 to 1990 were reviewed. Pathology was centrally reviewed in 54 cases. Histology, tumor size, grade, nodal status, age, menopausal status, history of benign breast disease, extent of surgery, resection margins, and radiation dose were each examined as potential prognostic factors by univariate analysis. To allow an analysis of radiation dose, total dose was normalized to a daily fraction size of 2 Gy. RESULTS: The median age at diagnosis was 50.5 years (13-82 years). The pathologic diagnosis was found to be malignant cystosarcoma phyllodes in 32 patients, with the remainder being stromal sarcoma (14), angiosarcoma (8), fibrosarcoma (7), carcinosarcoma (5), liposarcoma (4), other (8). Eighteen patients had grade I or II tumors, 43 had grade III or IV, and 18 were not evaluable. The 5- and 10-year actuarial rates for all 78 patients were 57% and 48% for cause-specific survival (CSS), and 47% and 42% for the relapse-free rates (RFR), respectively. The local relapse-free rate (LRFR) was 75% at both 5 and 10 years. The 5-year CSS for grade I or II tumors was 84% versus 55% for grade III or IV tumors (p = 0.01). Conservative surgery versus mastectomy did not lead to statistically significant different outcomes for CSS, RFR, or LRFR. The comparison of positive versus negative margins showed a 5-year LRFR of 33% versus 80% (p = 0.009). Pairwise comparisons of the 5-year CSS of 91% for > 48 Gy versus either 50% for < or = 48 Gy or 50% for no radiation showed p-values of 0.03 and 0.06, respectively. CONCLUSION: The authors propose that if negative surgical margins can be achieved, breast sarcoma should be managed by conservative surgery with postoperative irradiation to a microscopic tumoricidal dose (50 Gy) to the whole beast, and at least 60 Gy to the tumor bed. The decision to treat should be preceded by a preoperative multidisciplinary assessment. It is also recommended that an axillary lymph node dissection is not indicated, with the possible exception of patients with carcinosarcoma.

Papillary and follicular thyroid cancer: impact of treatment in 1578 patients.

We report the experience from 13 Canadian radiotherapy centres concerning the treatment and outcome for 1074 papillary and 504 follicular thyroid cancer patients followed for 4-24 years. Surgical resection was carried out in almost all patients; there was no correlation between the type of operation and recurrence or survival. Treatment with external irradiation (201 patients) radioiodine (214 patients), or both (107 patients) was used more often in poor prognosis patients than in those with good prognostic factors, and was effective in reducing local recurrences and improving survival, especially in patients with microscopic residual disease postoperatively. Treatment complications were common but rarely fatal. Thyroid cancer was the cause of death in over half of the papillary cancer deaths and in two-thirds of the follicular cancer deaths.

Results of radiotherapy for epithelial skin cancer of the pinna: the Princess Margaret Hospital experience, 1982-1993.

PURPOSE: To assess the treatment outcome, late toxicity, and prognostic factors for radiotherapy (RT) of carcinoma of the pinna. METHODS AND MATERIALS: The charts of 313 patients treated between 01/82 and 12/93 were retrospectively reviewed. There were 334 lesions treated: 201 basal cell carcinoma (BCC), 122 squamous cell carcinoma (SCC), and 11 basosquamous carcinoma. RT was most commonly given by orthovoltage X-rays (278 lesions) or electrons (39 lesions). The most frequently used dose prescriptions were 35 Gy in 5 fractions (123 treatments with median field size = 4.9 cm(2)), 42. 5-45 Gy in 10 fractions (67 treatments with median field size = 10.5 cm(2)), and 50-65 Gy in 20-30 fractions (42 treatments with median field size = 81 cm(2)).2 cm. RESUL TS: The actuarial 2- and 5-year local control rates were 86.6% and 79.2 %. Multivariate analysis revealed two factors to be statistically signi ficant for increased local failure: tumor size > 2 cm (hazard ratio [HR] = 2.66, 95% confidence interval [CI] = 1.16-6.08), and a low biological effective dose (BED) (for each decrease of 5 BED units, HR = 1.76, 95% CI = 1.07-2.88). The 5-year actuarial rate of significant Grade 4 late toxicity was 7.3%. Factors statistically significant for this endpoint on univariate analysis were tumor size (p = 0.035), T-stage (p = 0.02), field size (p = 0.05), fraction size (p = 0.003), and BED (p = 0.05). CONCLUSIONS: RT is an eff ctive treatment option for epithelial skin cancer of the pinna. Large t umor size and low BED were independently statistically significantly ass ociated with increased local failure. Dose-fractionation schedules usin g fraction sizes < 4 Gy may reduce the risk of necrosis and ulceration, particularly for field sizes > 5 cm2.