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.

Evidence for proliferation of erythroid progenitor cells in the absence of added erythropoietin.

The cellular mechanisms underlying the requirement of leukocyte conditioned medium for human erythroid colony formation has been studied. Using photographic methods it was found that erythroid progenitor cells were able to form small colonies in the absence of added erythropoietin (epo). The addition of epo at this time leads to further growth and hemoglobinization of cells within the colony. Leukocyte conditioned medium was found to be required for this early proliferative stage of erythroid colony formation.

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.

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.

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.

Non-Hodgkin's lymphoma of the thyroid gland: prognostic factors and treatment outcome. The Princess Margaret Hospital Lymphoma Group.

PURPOSE: Non-Hodgkin's lymphoma presenting in the thyroid gland is uncommon. A review of the Princess Margaret Hospital experience was performed to assess treatment outcome and prognostic factors in this rare extranodal presentation of localized lymphoma. METHODS AND MATERIALS: Fifty-two patients treated at the PMH between 1978 and 1986 were identified and their records reviewed retrospectively. Staging procedures revealed 16 patients with Stage I, 28 with Stage II, and eight with Stages III or IV disease. Five patients were treated on a protocol designed for anaplastic carcinoma of thyroid and they were excluded from detailed analysis. Of 39 patients with Stages I and II disease, 18 were treated with radiotherapy alone, three chemotherapy alone, and 18 combined modality therapy. Combined modality therapy was used mainly in patients with large tumor bulk. RESULTS: The overall 5-year actuarial survival and cause-specific survival were 56% and 64%, respectively. The overall relapse-free rate was 61% at 5 years. Among the 39 patients with Stages I and II disease, the 5-year actuarial survival, cause-specific survival, and relapse-free rate were 64%, 73%, and 66%, respectively. There were no significant differences in outcome between those treated with radiotherapy alone and those treated with combined modality therapy (cause-specific survival: p = 0.25, relapse: p = 0.06). A univariate analysis showed that the only variable to reach statistical significance was tumor bulk. Age was marginally significant while stage and histology were not statistically significant, possibly due to the fairly homogeneous distribution of patients in each of these variables. Patients with progression or relapse of lymphoma after initial treatment frequently died of disease. Isolated gastrointestinal relapses occurred in three cases, representing 27% of all relapses. CONCLUSION: Based on the above results, we recognize that the majority of patients with localized thyroid lymphoma require combined modality therapy and we recommend radiotherapy alone only for a small, select group of patients with Stage I disease and small tumor bulk.

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.

Radiation therapy for pituitary adenoma: treatment outcome and prognostic factors.

PURPOSE: Radiation therapy is often an integral part of postoperative treatment in patients with nonfunctional pituitary adenomas. The Princess Margaret Hospital (PMH) experience was reviewed and analyzed to establish the role of radiation therapy in local control relative to its complications, and to see if subgroups of patients with a greater or lesser risk of recurrence postsurgery can be defined. METHODS AND MATERIALS: Records of 160 patients with nonfunctional pituitary adenoma treated between 1972 and 1986 were reviewed retrospectively. The review focused on 128 patients treated with surgery and postoperative radiation as initial therapy. The median total dose was 45 Gy. Local tumor control was defined as lack of progression or recurrence of adenoma as assessed clinically and by imaging studies. The following factors were analyzed for prognostic significance in local tumor control: age, sex, direction of tumor extension, radiation dose, and preoperative tumor size as reflected by the radiation field size. Complications including hypopituitarism and second tumors were analyzed. Hypopituitarism was defined as requirement for permanent hormone replacement therapy. RESULTS: With a median follow-up duration of 8.3 years, the 10-year actuarial local control rate was 87% for the entire 160 patients and 91% for the 128 patients given postoperative radiation as initial treatment. For the 29 patients referred for treatment of recurrent tumor, the 10-year local control rate was 78%. Prognostic factors for local control identified in univariate analysis included age (p = 0.005) and radiation field size (p = 0.0001). Older patients and those with larger tumors requiring large radiation portals were less likely to achieve durable local control. These two factors remained significant in a multivariate analysis (p < 0.005). The major complication, hypopituitarism requiring hormonal replacement with thyroxine, glucocorticoid, and sex hormone was observed to date in 65% (100 out of 155), 68% (105 out of 154), and 67% (85 out of 127) of evaluable patients, respectively. Radiation was the contributing cause of the hypopituitarism in only 23%, 16%, and 13%, respectively. There were no cases of brain necrosis or radiation damage to the optic pathways. Two patients developed a fatal in-field glioma of the brain stem at 10 and 15 years following radiation. CONCLUSION: Postoperative external beam radiation therapy is highly effective in preventing recurrence of hormonally inactive pituitary adenomas. Hypopituitarism is commonly observed, but radiation can only be incriminated as the contributing cause in approximately one-fifth of the cases. Treatment of patients at the time of recurrence gave comparable local control rates to those irradiated initially. Favorable patients (age < or = 50, with small tumors removed totally) probably can be safely observed postoperatively with radiation reserved for recurrence.

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.

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.

Proliferation measurements with flow cytometry Tpot in cancer of the uterine cervix: correlation between two laboratories and preliminary clinical results.

PURPOSE: To assess the prognostic value of the pretreatment potential doubling time (Tpot) in carcinoma of the uterine cervix, relative to other established clinical factors. METHODS AND MATERIALS: Fifty-two patients with cervical cancer were studied prospectively from March 1991 to October 1993. Pretreatment evaluation included examination under anesthesia and tumor biopsy 6 h following the intravenous administration of bromodeoxyuridine (200 mg). Tpot was determined by deriving the labeling index (LI) and S-phase synthesis time (Ts) using flow cytometry. Six patients were not evaluable and excluded. The remaining 46 patients (average age 55 years) were treated uniformly with radical radiation therapy. There were 39 squamous carcinomas and 7 adenocarcinomas. Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) stages were: Ib and IIa, 12 patients; IIb, 18 patients; III and IV, 16 patients. The median external beam dose was 50 Gy (range, 45-52.8 Gy) delivered in 25 fractions. The median intracavitary dose was 40 Gy (range. 25.5-40 Gy) delivered with a single line source to a point 2 cm lateral of the midline, with a mean dose rate of 0.71 Gy/h. The median overall treatment time was 45 days (range, 34-73 days). As of July 31, 1994, 12 patients had died of disease, and the average follow-up for alive patients was 1.4 years (range, 0.5-3.3 years). RESULTS: There were 27 tumors with diploid deoxyribonucleic acid (DNA) content and 19 tumors were aneuploid. The median and mean Tpot for the 46 patients were 5.5 and 6.6 days, respectively [range, 2.0-25.6 days; coefficient of variation (CV), 74%]. For 25 patients where Tpot measurements were performed at two separate laboratories, there was a fair correlation (r = 0.74), but systematic differences were detected suggesting that the lack of agreement was not simply due to intratumoral variation. To date, 30 patients remained disease free, while 8 patients had pelvic failure and 9 patients developed distant metastases as the first failure site (1 patient developed both at the same time). In univariate analysis, the only significant prognostic factor for disease-free survival was tumor size (p = 0.004). A short Tpot (or high LI) and long overall treatment time (OTT) were weakly associated with poorer disease-free survival, although not statistically significant (1/Tpot, p = 0.14; LI, p = 0.23; OTT, p = 0.04). Age, FIGO stage, hemoglobin level, S-phase fraction, DNA ploidy, and Ts were not associated with disease-free survival. Multiple regression analysis was not performed because of the relatively small number of patients and short follow-up. CONCLUSIONS: Tpot values determined with current techniques by different laboratories cannot be used interchangeably for the purpose of therapy decisions. Vigorous quality assurance and standardization of the laboratory procedures and analysis methods are important to reduce interlaboratory variation. In this uniformly treated group of patients with cancer of the uterine cervix, traditional clinical prognostic factors remain the most important. Preliminary data suggest that the flow cytometry-determined Tpot and labeling index predict for disease-free survival, although a larger number of patients with longer follow-up is required to assess the true prognostic significance of these assays and to determine if their effect is independent of other clinical factors.

External radiation therapy in the treatment of thyroid malignancy.

The use of external beam radiation therapy in the management of thyroid malignancy is reviewed. Information from retrospective studies is presented and critically appraised as to the situations in which radiotherapy may be of benefit when used as part of initial treatment in the various thyroid malignancies. in particular, the role of external beam radiation and adjuvant treatment in addition to iodine-131 in differentiated thyroid cancer in medullary thyroid cancer are discussed.

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.

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.

Role of radiation therapy in clinical hormonally-active pituitary adenomas.

BACKGROUND AND PURPOSE: The outcome following radiation therapy (RT) of hormonally-active pituitary adenomas was assessed. The purpose of this analysis was to determine the control rate after radiation, identify any prognostic factors and evaluate the late toxicity. MATERIALS AND METHODS: From 1972 to 1986, 145 patients received RT for hormonally-active pituitary adenomas. The median age was 39 years (range 15-76), with 81 males and 64 females. There were 52 patients with acromegaly, 64 with prolactinoma, and 29 with Cushing's disease. The median follow-up was 7.3 years. RT was given as primary treatment in 17 patients, after initial surgery in 65 patients, and as part of salvage therapy in 63 patients. The median total dose was 50 Gy (daily fraction: 2 Gy). Tumor control was defined as normalization of basal hormonal level and lack of progression of adenoma assessed by imaging studies. The following factors were analyzed for prognostic significance in tumor control: age, sex, tumor type, direction of tumor extension, radiation dose, and radiation field size. RESULTS: The 10-year actuarial proportion of patients with persistent elevated hormone level were 61% following RT alone, and 44% with the addition of medical management. The progression-free rate was 96% at 10 years. Of the 20 deaths, three patients died with uncontrolled pituitary adenoma and three died of treatment complications. The actuarial 10-year overall and cause-specific survival rates were 86% and 97%. The actuarial rates of radiation-induced hypopituitarism were 35%, 22% and 22% at 10 years for thyroid, glucocorticoid and gonadal functions, respectively. None of the factors examined were found to be significant predictors of tumor control. CONCLUSIONS: Post-operative external beam RT is highly effective in preventing recurrence of space-occupying effects of hormonally-active pituitary adenomas. However, long-term biochemical remission is observed only in approximately 40% of patients (at 10 years), with an additional 20% requiring medical therapy. Malignancies of the CNS can develop as an infrequent late event.

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.