Early-stage mantle cell lymphoma: a retrospective analysis from the International Lymphoma Radiation Oncology Group (ILROG).

BACKGROUND: Mantle cell lymphoma (MCL) rarely presents as early-stage disease, but clinical observations suggest that patients who present with early-stage disease may have better outcomes than those with advanced-stage disease. PATIENTS AND METHODS: In this 13-institution study, we examined outcomes among 179 patients with early-stage (stage I or II) MCL in an attempt to identify prognostic factors that influence treatment selection and outcome. Variables examined included clinical characteristics, treatment modality, response to therapy, sites of failure, and survival. RESULTS: Patients were predominantly male (78%) with head and neck being the most common presenting sites (75%). Most failures occurred outside the original disease site (79%). Although the administration of radiation therapy, either alone or with chemotherapy, reduced the risk of local failure, it did not translate into an improved freedom from progression or overall survival (OS). The treatment outcomes were independent of treatment modality. The 10-year OS for patients treated with chemotherapy alone, chemo-radiation therapy and radiation therapy alone were 69%, 62%, and 74% (P = 0.79), and the 10-year freedom from progression were 46%, 43%, and 31% (P = 0.64), respectively. CONCLUSION: Given the excellent OS rates regardless of initial therapy in patients with early-stage MCL, de-intensified therapy to limit treatment-related toxicity is a reasonable approach.

Thyroid cancer patients' involvement in adjuvant radioactive iodine treatment decision-making and decision regret: an exploratory study.

PURPOSE: We explored regret in thyroid cancer patients, relating to the decision to accept or reject adjuvant radioactive iodine treatment. METHODS: We studied patients with a recent diagnosis of early stage papillary thyroid carcinoma, in whom treatment decisions on adjuvant radioactive iodine had been finalized. Participants completed a Decision Regret Scale questionnaire. We asked the participants to identify who made the final decision about radioactive iodine treatment. We explored the relationship between decision regret and a) degree of patient involvement in decision-making and b) receipt of radioactive iodine treatment. RESULTS: We included 44 individuals, more than half of whom received adjuvant radioactive iodine treatment (26/44). Decision regret was generally low (mean 22.1, standard deviation [SD] 13.0). Participants reported that the final treatment decision was made by the following: patient and doctor (52.3%, 23/44), completely the patient (27.3%, 12/44), or completely the physician (20.5%, 9/44). Decision regret significantly differed according to who made the final decision: the patient (mean 19.0, SD 11.3), patient and doctor (mean 19.5, SD 7.4), and the doctor (mean 32.9, SD 20.37) (F = 4.569; degrees of freedom = 2, 41; p = 0.016). There was no significant difference in decision regret between patients who received radioactive iodine and those who did not (mean difference -2.5; 95% confidence interval -10.6, 5.6; p = 0.540). CONCLUSION: Thyroid cancer patients who reported being involved in the final treatment decision on adjuvant radioactive iodine had less regret than those who did not.

How can we meet the information needs of patients with early stage papillary thyroid cancer considering radioactive iodine remnant ablation?

In patients with early stage papillary thyroid carcinoma (PTC) who have had a thyroidectomy, the decision must be made to accept or reject radioactive iodine remnant ablation (RRA). Counselling patients about this decision can be challenging, given the medical evidence uncertainties and the complexity of related information. Although physicians are the primary source of medical information for patients considering RRA, some patients have a desire for supplemental information from sources such as the internet. Yet, thyroid cancer resources on the internet are of variable quality, and some may not be applicable to the individual case. We have developed a computerized educational tool [called a decision aid (DA)], directed to patients with early stage papillary thyroid cancer, and intended as an adjunct to physician counselling, to relay evidence-based medical information on disease prognosis and the choice to accept or reject RRA. DAs are tools used to inform patients about available treatment options and have been utilized in oncologic decision-making. We tested our web-based DA in fifty patients with early stage PTC and found that it improved medical knowledge. Furthermore, participants found the technical usability of the tool acceptable. We are currently conducting a randomized controlled trial comparing the use of the DA plus usual care to usual care alone to confirm the educational benefit of the website and examine its impact on the decision-making process. In the future, DAs may play an expanded role as an adjunct to physician counselling in the care of patients with thyroid cancer.

An audit of imaging test utilization for the management of lymphoma in an oncology hospital: implications for resource planning?

The purpose of this study was to assist with resource planning by examining the pattern of physician utilization of imaging procedures for lymphoma patients in a dedicated oncology hospital. The proportion of imaging tests ordered for routine follow up with no specific clinical indication was quantified, with specific attention to CT scans. A 3-month audit was performed. The reasons for ordering all imaging procedures (X-rays, CT scans, ultrasound, nuclear scan and MRI) were determined through a retrospective chart review. 411 lymphoma patients had 686 assessments (sets of imaging tests) and 981 procedures (individual imaging tests). Most procedures were CT scans (52%) and chest radiographs (30%). The most common reasons for ordering imaging were assessing response (23%), and investigating new symptoms (19%). Routine follow up constituted 21% of the assessments (142/686), and of these, 82% were chest radiographs (116/142), while 24% (34/142) were CT scans. With analysis restricted to CT scans (296 assessments in 248 patients), the most common reason for ordering CT scans were response evaluation (40%), and suspicion of recurrence and/or new symptom (23%). Follow-up CT scans done with no clinical indication comprised 8% (25/296) of all CT assessments. Staging CT scans were under-represented at 6% of all assessments. Imaging with CT scans for follow up of asymptomatic patients is infrequent. However, scans done for staging new lymphoma patients were unexpectedly low in frequency, due to scans done elsewhere prior to referral. This analysis uncovered utilization patterns, helped resource planning and provided data to reduce unnecessary imaging procedures.

Is there a relationship between repopulation and hypoxia/reoxygenation? Results from human carcinoma of the cervix.

Long overall treatment times are detrimental for cure by radiotherapy and it has been argued that this may be due to repopulation occurring during the course of treatment. However, attempts to predict treatment outcome in relation to tumour proliferation, using pretreatment measurements of kinetic parameters such as Tpot or labelling index (LI) have not met with great success. One possible reason is that hypoxia/reoxygenation is linked to the growth of the tumour and its ability to repopulate. Data from studies in animal models have provided support for this possibility. We made measurement of tumour hypoxia, reoxygenation during treatment and pretreatment measurements of both Tpot and LI in groups of patients with cervix carcinoma undergoing radical radiation treatment. The data show a relationship between pretreatment pO2 measurements and treatment outcome, but reoxygenation did not show any association with treatment outcome. There was no significant association between pretreatment kinetic parameters and treatment outcome, nor was there any evidence of a relationship between pretreatment kinetic parameters and pO2. In the small group of 28 patients whose tumours underwent measurements of both pretreatment kinetic parameters (Tpot, LI) and reoxygenation, there was no relationship between these two sets of measurements. There was also no evidence that a combination of kinetic and reoxygenation measurements could be predictive of treatment outcome.

Evolution of treatment for Hodgkin's disease: a population-based study of radiation therapy use and outcome.

AIM: To examine changes in radiotherapy (RT) use, cause-specific survival (CSS), and overall survival (OS) in a population-based cohort of Hodgkin's disease (HD) patients diagnosed from 1982 to 1996. MATERIALS AND METHODS: Adult patients with HD diagnosed from 1 January 1982 to 31 December 1996 (n = 3957) were identified from the Ontario Cancer Registry. The cohort was divided into three consecutive 5-year periods: 1982-1986, 1987-1991, and 1992-1996. RT use, CSS and OS in each of these three periods were compared. For the entire cohort, the cumulative incidence of different causes of death was calculated. RESULTS: The proportion of patients receiving RT within 11 weeks of diagnosis declined over the three consecutive periods (25.1%, 15.6%, 11.7%, P < 0.001), as did the proportion receiving RT within 45 weeks (57.0%, 51.0%, 48.1%; P < 0.001). There was a significant increase in 5-year CSS over time (81%, 87%, 89%; P < 0.001), and OS (72%, 77%, 82%; P < 0.001), which remained significant in multivariable analyses. The cumulative incidence of death from causes other than HD was equal to the incidence of HD-related death within 12 years of diagnosis. CONCLUSIONS: There was a significant decline in the use of RT as the primary treatment modality and as part of the initial management of HD from 1982-1996 in Ontario. A greater proportion of patients received their RT after a delay consistent with the receipt of prior chemotherapy. There was also a significant increase in the CSS and OS over this period. These findings are in keeping with the adoption of effective chemotherapy in the treatment of HD.

Stage I and II MALT lymphoma: results of treatment with radiotherapy.

PURPOSE: Mucosa-associated lymphoid tissue (MALT) lymphoma is a distinct disease with specific clinical and pathologic features that may affect diverse organs. We analyzed our recent experience with Stage I/II MALT lymphoma presenting in the stomach and other organs to assess the outcome following involved field radiation therapy (RT). PATIENTS AND METHODS: Seventy patients with Stage IE (62) and IIE (8) disease were treated between 1989 and 1998. Patients with transformed MALT were excluded. The median age was 62 years (range, 24--83 years), M:F ratio 1:2.2. Presenting sites included stomach, 15; orbital adnexa, 19; salivary glands, 15; thyroid, 8; lung, 5; upper airways, 3 (nasopharynx, 2; larynx, 1); urinary bladder, 3; breast, 1; and rectum, 1. Staging included site-specific imaging, CT abdomen in 66 patients (94%) and bone marrow biopsy in 54 (77%). Sixty-two patients received radiation therapy: 52 received RT alone, 7 received chemotherapy and RT, and 3 received antibiotics followed by RT. Median RT dose was 30 Gy (range, 17.5--35 Gy). Most frequently used RT prescriptions were 25 Gy (26 patients-18 orbit, 6 stomach, and 2 salivary glands), 30 Gy (23 patients), and 35 Gy (8 patients). Five patients had complete surgical excision of lymphoma and no other treatment (stomach 1, salivary 2, lung 2), whereas 2 patients with gastric lymphoma received antibiotics only. One patient refused treatment and was excluded from the analysis of treatment outcome, leaving 69 patients with a median follow-up of 4.2 years (range, 0.3-11.4 years). RESULTS: A complete response was achieved in 66/69 patients, and 3 patients had partial response (2 lung, 1 orbit). The 5-year disease-free survival (DFS) was 76%, and the overall survival was 96%. No relapses were observed in patients with stomach and thyroid lymphoma. The 5-year DFS for these patients was 93%, in contrast to 69% for patients presenting in other sites (p = 0.006). Among the 5 patients treated with surgery only, 2 relapsed locally (lung, and minor salivary gland). Among 62 patients who received RT, 8 relapsed (2 salivary, 3 orbit, 1 nasopharynx, 1 larynx, 1 breast). Three patients relapsed in the nonirradiated contralateral paired organ, 4 in distant sites, and 1 in both local and distant sites. The overall local control rate with radiation was 97% (60/62 patients). CONCLUSION: Localized MALT lymphomas have excellent prognosis following moderate-dose RT. Gastric and thyroid MALT lymphomas have better early outcome, as compared to the other sites where distant failure is more common. Relapses were observed in nonirradiated paired organs or distant sites. Further follow-up is required to assess the impact of failure on survival.

The effects of gum chewing, four oral hygiene procedures, and two saliva collection techniques, on the output of bacteria into human whole saliva.

Six healthy dentate individuals collected a 5-min sample of unstimulated whole saliva (UWS) and dilutions were plated out on blood agar and grown anaerobically for 48 h. The output of bacteria into saliva (counts/min) was calculated as the product of counts/ml and ml/min. The individuals repeated the collections at intervals of up to 7 h after (1) rinsing with water, (2) eating a meal plus tooth brushing, (3) a thorough dental prophylaxis, or (4) tongue brushing and scraping. They also collected saliva at intervals while chewing gum for 20 min, as did 10 individuals who chewed gum for 2 h. The original six individuals also collected UWS under "drooling" (no oral movements) and "spitting" conditions. Six edentulous individuals not wearing their dentures collected UWS before and after a water rinse. With the four oral hygiene procedures, bacterial outputs fell initially and then rose again, but a repeated-measures ANOVA revealed no significant differences in the effects of the four procedures. Gum chewing caused initial marked increases in the outputs of bacterial and epithelial cells, but these fell with time and reached a plateau after about 10 min at outputs above those in UWS. Samples collected by spitting contained up to 14 times more bacteria than those collected by drooling. Bacterial output by edentulous individuals did not differ from that in those with teeth. It is concluded that bacteria from the teeth and gingival crevices normally make only a small contribution to those in saliva, that various oral hygiene procedures have similar effects on bacterial output into saliva, and that saliva collection conditions should be standardized and specified.

Solitary plasmacytoma treated with radiotherapy: impact of tumor size on outcome.

PURPOSE: Solitary plasmacytoma (SP) is a rare presentation of plasma cell neoplasms. In contrast to multiple myeloma, long-term disease-free survival and cure is possible following local radiotherapy (RT), particularly for soft tissue presentations. In this study, we attempt to identify factors that predict for local failure, progression to multiple myeloma, and disease-free survival (DFS) in patients mainly managed with local RT. METHODS AND MATERIALS: We identified 46 patients referred to the Princess Margaret Hospital between 1982 and 1993. The median age was 63 years (range 35-95), with a male:female ratio of 1.9:1. All patients had biopsy-proven SP (osseous: 32, soft tissue: 14). M-protein was abnormal in 19 patients (41%). All patients were treated with local RT (median dose 35 Gy), with 5 patients (11%) also receiving chemotherapy. Maximum tumor size pre-RT ranged from 0 to 18 cm (median 2.5). RESULTS: The 8-year overall survival, DFS, and myeloma-free rates were 65%, 44%, and 50%, respectively. The local control rate was 83%. Factors predictive of progression to myeloma (and poorer DFS) included bone presentation and older age. However, these two factors did not influence local control, which was affected by tumor size. All tumors < 5 cm in bulk (34 patients) were controlled by RT. Anatomic location did not predict outcome; however, 3 of the 5 tumors arising in paranasal sinuses did not achieve local control. Lower RT dose (< or =35 Gy) was not associated with a higher risk of local failure. CONCLUSION: Solitary plasmacytomas are effectively treated with moderate-dose RT, although osseous tumors have a high rate of recurrence as systemic myeloma. Large tumor bulk locally (> or =5 cm) predicts for local failure. Combined chemotherapy and RT should be investigated in these high-risk patients to increase the local control rate and the cure rate.

Management of localized (stage I and II) clinically aggressive lymphomas.

The treatment for non-Hodgkin's lymphomas is chiefly dependent on the histologic type and the anatomic extent of the disease, reflected by the stage. In the past 30 years, the treatment of localized large cell lymphomas has evolved from the use of radiotherapy (RT) alone to the routine use of combined modality therapy (CMT). Randomized controlled trials have shown superiority of the CMT approach as compared to RT alone, or chemotherapy alone. The data will be critically appraised in this review. Currently, approximately two-thirds of patients with stage I and II clinically-aggressive lymphomas will be cured with initial planned combined modality therapy. The clinical prognostic factors predicting refractory or relapse disease are now clearly recognized, and they are: older age, stage II disease, high lactate dehydrogenase (LDH), poor performance status, and bulky disease. Patients with poor-risk features are candidates for clinical trials to examine the potential benefits of initial treatment intensification programs. Elderly patients over the age of 60 years account for about half of the patients with lymphoma, and they may tolerate therapy less well. They are a special subgroup where prospective studies are required to determine the optimal management.

Daily general anaesthesia for radiotherapy in unco-operative patients: ingredients for successful management.

An unco-operative patient requiring daily radiation therapy presents a difficult clinical problem. After reviewing the paediatric oncology literature addressing the use of general anaesthesia for short medical procedures, we have developed checklists of procedural guidelines and monitoring equipment for the safe use of daily anaesthesia in adult patients who require a fractionated course of radiation therapy. We illustrate this by describing the successful treatment of a woman with autism and Hodgkin's disease who required daily general anaesthesia for immobilization during a 4-week course of radiation therapy. Propofol was used as the primary drug and was not associated with any adverse side-effects. There was no development of tolerance.

Proliferation parameters in epidermoid carcinomas of the anal canal.

PURPOSE: In a prospective study, we assessed the proliferation parameters in primary epidermoid carcinomas of the anal canal, and results were compared with those in cervical carcinomas. METHODS: Between January 1992 and December 1996, 32 patients with primary epidermoid carcinoma of the anal canal were studied prospectively. Patients were given i.v. bromodeoxyuridine and proliferation parameters were obtained using flow cytometry. The treatment protocol consisted of radiation therapy (XRT) (24 Gy/12-3.5 week split-28 Gy/14) and concurrent 5-fluorouracil and mitomycin C. Proliferation parameters were not obtained in six patients, leaving 26 patients in the analysis. There were 16 females and ten males, with two T1, 16 T2, five T3 and three T4 lesions. Median follow-up was 3.6 years. There were 22 squamous cell and four basaloid carcinomas. Six tumors were aneuploid. RESULTS: Median values for T(s) and S-phase fraction were 7.7 h and 8.2%, respectively. The median LI was 6.8% (0.9-35.7%), and the median T(pot) was 4.1 days (0.9-30 days). There was no correlation of LI or T(pot) with gender, age, tumor stage, size or histology. Local failure was observed in five patients (T(pot)>4.1 days, n=3; LI>6.8%, n=4). Isolated regional failure or distant disease in the absence of local failure was not observed. The small number of outcome events precluded a definitive analysis of the prognostic role of LI and T(pot). Values for the proliferation parameters were similar to those in our updated study of patients with carcinoma of the uterine cervix (n=107), median LI of 6.7% and median T(pot) of 5.5 days. CONCLUSIONS: We conclude that proliferation parameters in anal carcinomas are similar to those in cervical carcinomas. Rapid tumor proliferation does not have an apparent adverse impact on outcome in anal carcinomas managed by split-course XRT with concurrent 5-florouracil and mitomycin C.

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.

Interrelationship of proliferation and hypoxia in carcinoma of the cervix.

PURPOSE: In human cervix cancer treated with radiotherapy, we have previously shown from separate groups of patients that tumor hypoxia and proliferation rate as measured by bromodeoxyuridine (BrdU) labeling index (LI) are important determinants of clinical outcome. We now examine the relationship of these two pre-treatment predictive assays in 43 patients studied prospectively from 1994-98 where both tests were performed for each patient. MATERIAL AND METHODS: Newly diagnosed patients with carcinoma of the cervix were examined under anesthesia for staging purposes. Patients were given BrdU (200 mg) by intravenous route prior to the procedure. Tumor oxygenation was measured with the Eppendorf pO2 histograph. Biopsy of tumor was then performed and the BrdU LI was obtained by flow cytometry. The degree of tumor hypoxia for each tumor was expressed as median pO2 values, and as the percentage of pO2 readings <5 mm Hg (HP5). RESULTS: The median age was 53 years (range 23-79 years). There were 32 squamous, and 11 non-squamous carcinomas. FIGO stages were: IB and IIA, 8; IIB, 17; IIIB, 18; with a median tumor size of 6 cm (range 2-10 cm). The patients received uniform treatment with radical radiation therapy. There were 22 diploid and 21 aneuploid tumors. The median LI, pO2, and HP5 were 8.0%, 5.4 mm Hg, and 46.8%, respectively. Tests for linear associations showed no significant correlation between median pO2 vs. LI (r = 0.078, p = 0.62), and HP5 vs. LI (r = -0.14, p = 0.38). CONCLUSIONS: The clinical outcome in this group of patients is immature, but these results suggest that tumor hypoxia and proliferation measurements are independent and potentially complementary predictive assays in cervix carcinoma. Further investigations are required to examine the distribution of proliferating tumor cells and its relationship with hypoxic tumor cells in tissue sections with the use of immunohistological techniques and image analysis systems.

Tumor proliferation and apoptosis in human uterine cervix carcinoma I: correlations between variables.

PURPOSE: Parameters for tumor proliferation and apoptosis were studied prospectively in 84 previously untreated patients with a diagnosis of carcinoma of the uterine cervix. MATERIALS AND METHODS: Tumor proliferation was assessed by in vivo labeling with bromodeoxyuridine (BrdU), followed by a biopsy of the tumor 4-10 h thereafter during an examination under anesthesia. The potential doubling time (Tpot) was obtained by deriving the BrdU labeling index (LI) and S-phase duration (Ts) using flow cytometry. The LI for BrdU and its staining pattern were also determined immunohistochemically. Apoptosis was assessed histologically using morphological criteria. RESULTS: Seven patients were excluded and the FIGO stages of the remaining 77 patients were as follows: IB and IIA, 20 patients; IIB, 29 patients; IIIB and IV, 28 patients. The median tumor diameter was 6 cm. There were 61 squamous cell, 11 adeno- and five adenosquamous carcinomas. Of the 63 patients in whom the tumor grade could be determined, 37 were well or moderately well differentiated and the remaining 26 were poorly differentiated. The median mitotic index (MI) was 0.7%. There were 43 diploid and 34 aneuploid tumors. Median values for Ts and S-phase fraction (SPF) were 9.9 h and 16%, respectively. The median BrdU LI by flow cytometry (LI-fc) was 6.7%. There was a significant correlation between LI-fc and LI by histology, although values for the latter (median 11.1%) were consistently higher than those determined by flow cytometry by a factor of 1.5. The median Tpot value was 5.0 days. The median apoptotic index (AI) was 1.0% and AI correlated positively with LI-fc. Median values for LI-fc increased with increasing tumor size and were 5.1%, 6.4%, 7.5% and 11.0% for tumors measuring < or = 4 cm, 4-6 cm, 6-8 cm and > 8 cm, respectively. The remaining proliferation parameters, however, showed no correlation with tumor size, stage, grade or histologic type. CONCLUSIONS: In carcinomas of the cervix, tumor proliferation is positively associated with apoptosis and tumor size. These findings suggest that parameters for tumor proliferation and apoptosis are associated with tumor progression and may thus be predictive of clinical outcome.

Tumour proliferation and apoptosis in human uterine cervix carcinoma II: correlations with clinical outcome.

PURPOSE: The prognostic value of tumour proliferation and apoptosis measurements were studied prospectively in patients with carcinoma of the uterine cervix, relative to other established clinical factors. MATERIALS AND METHODS: The labelling index (LI) for bromodeoxyuridine was determined by flow cytometry (fc) and also by immunohistochemistry. Apoptosis was assessed histologically using morphological criteria. Patients were treated with radical radiation therapy (RT). RESULTS: The median/mean LI-fc were 6.7%/7.9% (range 1.52-3.9%). The median/mean apoptosis index (AI) were 1.0%/1.6% (range 0-6.8%). To date, 27 patients have died of disease, and the median follow-up for alive patients is 3.2 years (range 0.4-6.0 years). Among 64 patients who completely responded to treatment, 25 patients have relapsed (six pelvic, 17 distant and two pelvic and distant). In univariate analysis, the most significant factors for disease-free survival (DFS) were large tumour size (P=0.0001), low haemoglobin (P=0.01 ), LI-fc (DFS 67% for LI < 7%, 33% for LI > or = 7%, P=0.03), and T(pot) (DFS 66% for T(pot) > 5 days, 35% for T(pot) < or = 5 days, P=0.04) Stage, overall treatment time (OTT), S-phase fraction, ploidy, T(s), LI by histology, mitotic index, and AI were not significant. Multivariate analysis (Cox's model) showed that the only significant prognostic factors for DFS were tumour size and OTT. However, for small tumours (diameter < 6 cm), either a high LI-fc ( > or = 7%) or a high AI ( > 1%) was associated with poorer DFS, whereas patients with larger tumours (diameter > or = 6 cm) fared poorly regardless of LI-fc and AI. CONCLUSIONS: Tumour size was the most important prognostic factor in cervix carcinoma. Although none of the biologic parameters have independent prognostic significance when the effect of initial tumour size was taken into account, our data suggests that LI and AI may be useful in discriminating outcome for patients with smaller tumours when managed by radical RT. These findings support the hypothesis that rapidly proliferating tumours are less likely to be controlled with a conventional course of RT.

Thoracic radiation therapy before autologous bone marrow transplantation in relapsed or refractory Hodgkin's disease. PMH Lymphoma Group, and the Toronto Autologous BMT Group.

The aim of this study was to assess the relationship between radiation therapy (RT) and treatment-related mortality in patients receiving high-dose chemotherapy (HDCT) and autologous bone marrow transplantation (ABMT) for recurrent/refractory Hodgkin's disease (HD). Between December 1986 and December 1992, 59 patients previously treated at the Princess Margaret Hospital underwent HDCT (etoposide 60 mg/kg, melphalan 160 mg/m2) and ABMT, performed for refractory (13 patients) or relapsed (46 patients) HD. RT was incorporated in the salvage treatment with the intent to achieve complete control of disease prior to ABMT. RT was given before ABMT in 33 patients, and after ABMT in 4 patients. Treatment-related (TR) mortality was defined as any death occurring within 100 days of ABMT. Autopsies were performed for all patients with TR deaths. With a median follow-up of 4.6 years (range 1.2-7.4 years), the actuarial overall survival was 41% +/- 14% at 5 years. We observed 37 deaths, and 10 of these were TR deaths. Among the 24 patients who received thoracic RT before ABMT, there were 8 TR deaths, 3 of these solely attributable to radiation pneumonitis. The remaining 5 TR deaths all had respiratory failure with complicating sepsis as a major medical problem. The interval from RT to ABMT was shorter for 8 patients dying of TR death (mean 37 days; range 0-103 days), than for the 16 survivors (mean 105 days; range 0-263 days) (P = 0.026). Among 9 patients with ABMT within 50 days of thoracic RT, 6 had TR death. In contrast, among the 35 patients without thoracic RT (26 no RT, 9 non-thoracic RT), there were only 2 TR deaths. The 4 patients treated with mantle RT post-ABMT had no serious pulmonary complications. The use of thoracic RT before HDCT and ABMT was associated with a high post-transplant mortality rate. It was most evident in patients who received thoracic RT within 50 days prior to ABMT, or when the target volume included large volume of lung. We recommend that the use of post-transplant RT be investigated to decrease TR mortality.

External-beam radiation therapy in the treatment of differentiated thyroid cancer.

The role of external-beam radiation therapy (EBRT) in differentiated thyroid cancer is reviewed. In the presence of gross residual disease after attempted surgical excision, retrospective series have reported local control is possible with EBRT. If, in addition to Iodine-131 (I131), there is a role for adjuvant EBRT in differentiated thyroid cancer, it would be only in patients in whom there is a high risk of relapse in the thyroid bed. Evidence is presented that suggests that EBRT can improve the local relapse-free rate in selected patients (over the age of 45, with microscopic residual disease or extensive extrathyroid invasion). For patients with recurrence in the thyroid bed, EBRT can be given in addition to surgery and I131. In bone metastases that are demonstrable radiographically, I131 therapy is often unsuccessful and EBRT also should be given. The technique of thyroid bed radiation is described. EBRT has acceptable acute toxicity and rarely produces serious long-term complications.

Prescribing 131Iodine based on neck uptake produces effective thyroid ablation and reduced hospital stay.

PURPOSE: The aim of this study was to determine if thyroid cancer patients with low percentage neck uptake of iodine on postoperative thyroid scans can be treated with lower doses of 131Iodine while maintaining a high ablation rate. MATERIALS AND METHODS: We reviewed the records of 58 patients with differentiated thyroid cancer treated with 131I at the Princess Margaret Hospital. The activity of 131I was prescribed based on the 48 h percentage neck uptake in postoperative thyroid scans. Patients with < or =2% uptake received 1.07 GBq, patients with 2.1-4% uptake received 1.85 GBq, patients with 4.1-6% uptake received 2.80 GBq, patients with 6.1-8% uptake received 3.70 GBq and patients with >8% uptake received 4.60 GBq. When the scan suggested cervical lymph node metastases or residual tumor, 7.40 GBq was prescribed. Follow-up scans were performed at least 5 months after 131I therapy. Successful ablation was defined as the absence of visible uptake in the neck above background. RESULTS: Forty-nine patients were included in this analysis. The ablation rate according to the prescribed activity was as follows: 1.07 GBq, 16/20 (80%); 1.85 GBq, 4/5 (80%); 2.80 GBq, 1/1 (100%); 3.70 GBq, 0/1 (0%); 4.60 GBq, 7/8 (88%); 7.40 GBq, 13/14 (93%). The ablation rate for all patients treated on the protocol was 41/49 (84%, 95% CI 70-93%). For the group treated for remnant ablation, the overall ablation rate was 28/35 (80%, 95% CI 63-92%). Twenty-two (38%) of the 58 eligible patients received 1.07 GBq as outpatients. This saved 38 hospitalization days compared to a policy of treating all patients requiring remnant ablation with 3.70 GBq. CONCLUSIONS: We conclude that patients with less iodine uptake in postoperative thyroid scans can receive lower activities of 131I, allowing a significant proportion of patients to be treated on an outpatient basis while maintaining a high ablation rate.

Parathyroid carcinoma--the Princess Margaret Hospital experience.

PURPOSE: Carcinoma of the parathyroid gland is a rare disease representing 0.5 to 4% of patients with primary hyperparathyroidism. We reviewed our experience with this disease, with special emphasis on the role of adjuvant postoperative radiotherapy. METHODS: A retrospective review was conducted of all cases of parathyroid carcinoma referred to the Princess Margaret Hospital (PMH) from 1958-1996. Ten patients were identified. Their clinical features, management details, and treatment outcome are described. RESULTS: There were 5 men and 5 women with a mean age of 53 years. Of these, 7 patients underwent en bloc resection; among them, 4 had neck dissection or lymph node sampling. The other 3 patients underwent only limited surgery to remove the tumor. Seven patients were referred for consideration of adjuvant radiation treatment. Six patients were given adjuvant radiation therapy for microscopic residual disease. All patients tolerated the radiation treatment well, with minimal side effects. The 7 patients have been followed regularly with no evidence of recurrence and normal serum calcium. The mean follow-up for the 6 patients who had adjuvant radiotherapy was 62.3 months (range 12 to 156 months). The remaining 3 patients had metastatic disease and were referred for palliative radiotherapy. CONCLUSIONS: Our results in a small number of patients suggest local radiation therapy to the tumor bed may have eliminated the strong predilection for local recurrence of this disease, as reported by other investigators.