Localised lymphoma of bone: prognostic factors and treatment recommendations. The Princess Margaret Hospital Lymphoma Group.

Twenty seven adult patients with newly diagnosed non-Hodgkin's lymphoma localised to either bone (Stage IE) or bone and regional lymph nodes (Stage IIE) were treated between 1967 and 1988. Median age was 53 years and the commonest histology (21 patients) was diffuse histiocytic lymphoma. Twenty-four patients were treated radically: 15 with radiation therapy (XRT) alone and nine with chemotherapy plus radiation therapy (CMT). The cause specific survival for these patients was 56% at 5 years and 40% at 10 years. Survival was significantly better for patients treated by CMT (88% at 5 years) as compared to XRT alone (40% at 5 years, P = 0.03) and for age less than 60 (72% at 5 years) compared to greater than or equal to 60 (30% at 5 years, P = 0.018). Relapse-free rate was 27% at 5 years with XRT alone and 89% with CMT (P = 0.01). Risk factors for loco-regional relapse (seven cases) included: large tumour bulk, treatment by XRT alone and use of 'limited' radiation fields. No radiation dose-response relationship could be identified in this study. Long term local control and survival for localised lymphoma of bone were excellent after treatment by CMT but XRT alone was associated with unacceptably high local and distant failure rates.     

Early stage infradiaphragmatic Hodgkin's disease: results of radiotherapy and review of the literature.

PURPOSE: To assess the impact of modality therapy on long-term outcome for infradiaphragmatic Hodgkin's disease (IDHD). METHODS AND MATERIALS: During the period 1965-1997, 847 patients with early stage Hodgkin's disease (HD) were evaluated and treated at our institution, 20 of them had IDHD (2.4%). Patients characteristics: stage I, nine patients (five pathological stage (PS), and four clinical stage (CS)) and stage II: 11 patients (six PS and five CS). Two modalities of treatment were used: combined modality (CMT), consisting of chemotherapy followed by extended field radiotherapy or radiotherapy alone (XRT). All patients with CS or PS II, except in one case, were treated with CMT. Overall, 12 patients were treated with CMT and the remaining eight patients were treated with XRT. RESULTS: The relapse rate after initial treatment was 30%. Ten-year disease free survival (DFS) and 10-year cause-specific survival were 60% and 92%, respectively. There was a non-significant trend to a better DFS for the CMT group of patients (76% vs. 35% for the whole series and 100% vs. 24% for stage I patients). The four relapsed patients in the XRT group were inguino-femoral PS I. In four out of the six patients who relapsed (66%) the failure was located solely in the supradiaphragmatic area, outside of the radiation fields. CONCLUSIONS: In our experience, inguino-femoral stage I patients have a high relapse rate after XRT; consequently, CMT consisting of chemotherapy plus involved field radiotherapy should be recommended for early stage HD confined below diaphragm.     

Combined chemotherapy and radiation versus radiation alone in the management of localized angiocentric lymphoma of the head and neck.

BACKGROUND AND PURPOSE: To clarify the clinical benefit derived from the combined modality therapy (CMT) comprised of chemotherapy and involved-field radiotherapy (XRT) for stage I and II angiocentric lymphomas of the head and neck. MATERIAL AND METHODS: Of 143 patients with angiocentric lymphoma of the head and neck treated at the Yonsei Cancer Center between 1976 and 1995, 104 patients (XRT group) received involved-field XRT alone with a median dose of 50.4 Gy (range: 20-70 Gy), while 39 patients (CMT group) received a median three cycles (range: 1-6 cycles) of chemotherapy before starting involved-field XRT. The response rate, patterns of failure, complications, and survival data of the XRT group were compared with those of the CMT group. RESULTS: Despite a higher response rate, local failure was the most common pattern of failure in patients of the both groups. The patterns of failure, including the systemic relapse rate were not influenced by the addition of combination chemotherapy. Although both modalities were well tolerated by the majority of patients, aberrant immunologic disorders or medical illnesses, such as a hemophagocytic syndrome, sepsis, intractable hemorrhage, or the evolution of second primary malignancies were more frequently observed in patients of the CMT group. The prognosis of patients in the XRT group was relatively poor, with a 5-year overall actuarial survival rate of 38% and disease-free survival rate of 32%, respectively. However, their clinical outcome was not altered by the addition of systemic chemotherapy. Achieving complete remission was the most important prognostic factor on univariate and multivariate analyses, but treatment modality was not found to be a prognostic variable influencing survival. CONCLUSIONS: Involved-field XRT alone for angiocentric lymphoma of the head and neck was insufficient to achieve an improved survival rate, but the combination of chemotherapy and involved-field XRT failed to demonstrate any therapeutic advantage over involved-field XRT alone.     

Apoptosis and the Bcl-2 gene family -- patterns of expression and prognostic value in stage I and II follicular center lymphoma

PURPOSE: The prognostic significance of spontaneous levels of apoptosis and Bcl-2, Bax, and Bcl-x protein expression in follicular center lymphoma (FCL) is unknown. The objectives of this retrospective study were (1) to investigate the relationship between pretreatment apoptosis levels and long-term treatment outcome in patients with Stage I and II FCL; (2) to define the incidence and patterns of Bax and Bcl-x protein expression in human FC; and (3) to determine the relationship of Bcl-2, Bax, and Bcl-x expression with spontaneous apoptosis levels and clinical outcome in localized FCL. METHODS AND MATERIALS: Between 1974 and 1988, 144 patients with Stage I or II FCL were treated. Hematoxylin and eosin (H & E) stained tissue sections of pretreatment specimens were retrieved for 96 patients. Treatment consisted of regional radiation therapy (XRT) for 25 patients, combined modality therapy (CMT) consisting of combination chemotherapy and XRT for 57 patients, and other treatments for 14 patients. Median follow-up for living patients was nearly 12 years. The apoptotic index (AI) was calculated by dividing the number of apoptotic cells by the total number of cells counted and multiplying by 100. Expression of Bcl-2, Bax, and Bcl-x proteins was assessed using immunohistochemistry. RESULTS: The mean and median AI values for the entire group were 0.53 and 0.4, respectively (range: 0-5.2). The AI strongly correlated with cytologic grade, with mean AI values of 0.25 for grade 1, 0.56 for grade 2, and 0.84 for grade 3 (p < 0.0005; Kendall correlation). A positive correlation was present between grouped AI and grouped mitotic index (MI) (p = 0.014). For patients treated with CMT, an AI < 0.4 correlated with improved freedom from relapse (FFR) p = 0.0145) and overall survival (OS) (p = 0.0081). An AI < 0.4 did not correlate with clinical outcome for the entire cohort or for patients receiving XRT only. Staining of tumor follicles for the Bcl-2 protein was positive, variable, and negative in 73%, 15%, and 12% of cases, respectively. Positive staining of tumor follicles was observed in 96% of cases for both the Bax and Bcl-x proteins. Expression of Bcl-2, Bax, or Bcl-x did not correlate with AI or clinical outcome. CONCLUSION: The level of spontaneous apoptosis in pretreatment specimens correlates with cytologic grade of FCL and is a significant predictor of FFR and OS for patients with localized FCL receiving CMT.     

Stage I to IIB Hodgkin's disease: the combined experience at Stanford University and the Joint Center for Radiation Therapy

The treatment records of 180 patients with pathological stage (PS) IB to IIB Hodgkin's disease treated at Stanford University Medical Center (SUMC) or the Joint Center for Radiation Therapy (JCRT) were reviewed. Pretreatment characteristics were analyzed to assess their influence on survival and freedom from relapse (FFR). The two most important disease characteristics predictive of relapse were the number and type of B symptoms present and the mediastinal mass ratio (MMR). Patients with both fevers and weight loss had a 7-year survival and FFR of only 57% and 48%, respectively. The poor prognosis in this group was apparent for treatment with either radiation (XRT) alone or combined modality therapy (CMT). Patients with night sweats only had no adverse effect of B symptoms on outcome. Patients with a MMR greater than 1/3 had a 7-year FFR of only 58% after XRT, but 79% after CMT (P = .12). The 7-year survivals for these patients were 85% and 88%, respectively. CMT improved the FFR of the entire group of 180 patients when compared with XRT (7-year FFR 86% and 74%, respectively, P = .02); however, survival in the two treatment groups was similar (88% and 89%). Among patients treated with radiation alone, there was a similar survival and FFR irrespective of whether pelvic irradiation was included in the initial treatment fields.     

Clinical features and results of therapy for children with paraspinal soft tissue sarcoma: a report of the Intergroup Rhabdomyosarcoma Study

Soft tissue sarcomas of the paraspinal region comprised 3.3% (56 of 1,688) of the patients entered and eligible on Intergroup Rhabdomyosarcoma Studies I (IRS-I) and II (IRS-II) (1972 to 1984). These lesions tended to be greater than 5 cm in diameter at diagnosis, invaded the spinal extradural space, and were of the extraosseous Ewing's sarcoma or undifferentiated sarcoma subtype in 55% (30 of 56) of the cases. Patients with tumors in clinical groups II, III, and IV were treated with radiotherapy (XRT) and vincristine-dactinomycin (VA) or VA plus cyclophosphamide (VAC) +/- doxorubicin. Clinical group I patients treated on IRS-II did not receive XRT, while those on IRS-I were randomized to receive VAC +/- XRT. Forty-four of the paraspinal patients (79%) achieved a complete response (CR) compared with 77% (1,260 of 1,632) for patients with disease in other sites. Twenty-seven patients (55%) subsequently relapsed (five local, three regional, four local and distant, and 14 distant). The proportion of patients surviving 5 years by clinical group (stage) from I to IV were 50%, 50%, 62%, and 27%, respectively. Paraspinal patients had somewhat poorer survival than patients with disease in other sites, both in IRS-I and IRS-II; the percentage of paraspinal patients surviving 5 years was 50% and 52% for IRS-I and IRS-II, respectively, whereas these percentages were 55% and 63% for patients with disease in other sites. Histology did not influence the CR rate, but unexpectedly, patients who had embryonal rhabdomyosarcoma (RMS) had the poorest overall survival rate. We concluded that patients with paraspinal lesions may require extended-field radiation therapy to reduce the high local failure rate and more intensive chemotherapy to achieve better local and systemic tumor control.     

Primary non-Hodgkin's lymphoma of bone.

Primary non-Hodgkin's lymphoma of bone (PLB) constitutes approximately 5% of all extranodal non-Hodgkin's lymphoma (NHL) and 7% of primary bone tumors. The peak incidence for PLB is in the fifth decade, with a slight preponderance of males over females. The presenting symptoms usually consist of localized bone pain and occasionally a palpable mass. Most patients with PLB have B-cell tumors with a diffuse mixed-cell or diffuse large cell histology. While most patients present with early-stage disease, it is not clear whether such patients benefit from combined-modality therapy (CMT) consisting of radiation therapy (RT) and chemotherapy (CT) compared with either RT or CT alone. However, there is strong evidence that CMT is beneficial in the treatment of localized NHL, and these results might be applicable to the therapy for PLB. Nevertheless, only a phase III randomized, controlled clinical trial will determine whether CMT is superior to either CT or RT alone.     

Prostate-specific antigen and external beam radiation therapy in prostate cancer.

This study of 133 patients with localized prostate cancer (Stages A2 to C), treated by external beam radiation therapy (XRT), was undertaken for two reasons: (1) to investigate the usefulness of pretreatment serum prostate-specific antigen (PSA) levels in evaluating patients before XRT; and (2) to investigate post-XRT changes in PSA values and their likely clinical significance. It was found that pretreatment PSA values in patients with localized disease exhibit wide patient to patient variability with a greater than 100-fold difference between the lowest and highest values. Although mean PSA values were significantly higher in Stage C disease (51 patients; mean PSA, 17.3 ng/ml) than in Stage A2 disease (31 patients; mean PSA, 9.0 ng/ml), Stage B1 disease (23 patients; mean PSA, 9.1 ng/ml), or Stage B2 disease (28 patients; mean PSA, 10.6 ng/ml), individual values were of virtually no help in assigning individual patients to a clinical stage. PSA levels did not correlate with grade. After XRT, PSA values fell significantly and dramatically in virtually all patients (98%) by 3 months follow-up. Mean PSA fell from 12.5 to 2.6 ng/ml, and median PSA fell from 6.6 to 1.9 ng/ml. In most patients, PSA continued to fall up to 12 months after XRT and then stabilized at 21 months. Although PSA values fell dramatically after XRT, PSA was detectable in the serum of all patients. PSA values tended to transiently and mildly elevate during XRT. In a small proportion of patients, rising PSA values were observed after 6 months. The full significance of this requires further follow-up, of four such patients, one has relapsed. PSA is a more sensitive marker of prostatic radiation than prostatic acid phosphatase.     

Large cell lymphoma stage IA/IAE

Fifty-two patients with large cell lymphoma stage IA/IAE were retrospectively reviewed for the purpose of evaluation of treatment methods. All pathology slides were reviewed by one pathologist with a special interest in lymphoma. There were 24 patients at stage IA and 28 at stage IAE. Twenty-six patients were treated with radiation alone (10 IA, 16 IAE) and 26 patients were treated with radiation therapy and chemotherapy (13 IA, 13 IAE). Patients treated with radiation therapy alone and those with combined modality therapy (CMT) have similar survival curves with p values greater than 0.05. Recurrence patterns are similar for either method of treatment. While the majority of the literature recommends CMT for large cell lymphoma, our study of 52 patients reveals no difference in survival or recurrence patterns for these patients by either method of treatment. We recommend radiation therapy alone for stage IA/IAE large cell lymphoma, with chemotherapy held in reserve for failure.     

Ovarian cancer metastatic to the brain: What is the optimal management?

PURPOSE: To better define determinants of survival and optimal management strategies for patients with ovarian cancer and brain metastases. METHODS: A review of literature using Medline identified 15 case series of ovarian cancer patients with brain metastases (OBM). Each article was abstracted for survival data, and in all cases, the intervals between ovarian cancer diagnosis and brain metastasis identification, and between brain metastasis identification and last follow-up were recorded. Cases were categorized by patient characteristics and treatment modality for brain metastases. Estimated survival probabilities were plotted using the Kaplan-Meier method with differences between subgroups analyzed by the log-rank test. Cox proportional hazards model was used to identify independent prognostic factors age, number of metastasis, and treatment modality associated with survival. RESULTS: The median interval from ovarian cancer diagnosis to brain metastasis in 104 identified patients was 19.5 months. Brain metastasis was single in 43%, multiple in 41%, and not reported in 16% of cases. About 81.7% of patients were treated for their brain metastases using external radiation therapy (XRT), chemotherapy, and surgery. XRT was utilized in 76% of 104 patients and in 93% of treated patients. The most commonly used modalities were XRT alone (40%) and craniotomy and XRT (17%). The median survival (MS) for all patients regardless of treatment type was 6 months. Patients who received any treatment lived longer than those not receiving surgery/chemotherapy/XRT (MS; 7 months vs. 2 months, P = 0.0001). Patients with single brain metastasis had a longer median survival (21 months vs. 6 months, P = 0.049) when treated with craniotomy plus radiation and/or chemotherapy compared to treatment regimens that excluded craniotomy. In a multivariate analysis, only treatment type was significant in predicting survival. CONCLUSION: OBM portends a poor prognosis, however, long-term survival is possible. Patients appear to benefit from therapy, especially selected groups of OBM patients with single brain metastasis treated with radiation therapy and surgery.     

Brief chemotherapy, involved field radiation therapy, and central nervous system prophylaxis for paranasal sinus lymphoma.

Lymphoma of the paranasal sinus is a rare tumor characterized by bulky local disease, early systemic dissemination, and a propensity for central nervous system (CNS) spread. Treatment with radiation alone generally has been disappointing. Based on previous encouraging reports of initial brief chemotherapy followed by involved field radiation therapy (IFRT) for localized large cell lymphoma, four consecutive patients with paranasal sinus lymphoma were treated with 6 weeks of chemotherapy followed by IFRT and CNS prophylaxis. All patients had bulky localized disease and diffuse large cell lymphoma. Complete response was seen in all patients, and none have had a relapse (minimum follow-up, 25 months; range, 25 to 32 months). Chemotherapy and radiation therapy were well tolerated. One patient developed an osteogenic sarcoma in the radiation field 32 months after completion of therapy. Administration of early frequent chemotherapy followed by IFRT and CNS prophylaxis appears to be an effective treatment strategy for patients with localized large cell lymphoma of the paranasal sinuses.     

Impact of adjuvant chemotherapy on cosmesis and complications in Stages I and II carcinoma of the breast treated by biopsy and radiation therapy

Cosmesis and complication rates were examined in patients with early stage carcinoma of the breast treated by biopsy and radiation therapy with and without adjuvant chemotherapy in an attempt to determine the effect of chemotherapy upon these parameters. Between April 1, 1975 and June 1, 1980, 51 patients were treated with radiation therapy and adjuvant chemotherapy (XRT + ACT) and 83 patients with radiotherapy alone (XRT). Chemotherapy usually consisted of cytoxan, methotrexate and 5-fluorouracil for 6 or 12 cycles. Minimum follow-up was 36 months. Cosmetic results deteriorated with time in both groups but to a greater extent in the XRT + ACT group. At 36 months, excellent cosmetic results were obtained in 73 of the 83 patients (88%) in the XRT group compared to 37 of 51 patients (73%) in the XRT + ACT group (p = <.05). Comparison of the two treatment groups revealed that complication rates were significantly increased in the XRT + ACT group. Of the 51 patients in the XRT + ACT group, 21 patients (41%) suffered complications compared to 8 (10%) of the 83 patients in the XRT group (p = <.001). This difference in complication rates resulted primarily from an increased incidence in the XRT + ACT group of wet desquamation in the electron beam portal used to treat the internal mammary lymph nodes and a trend towards a higher incidence of spontaneous nonpathologic rib fractures, myositis and arm edema. An increased incidence of nonbreast primary cancers was not seen. Our preliminary conclusions are that adjuvant chemotherapy has a negative impact upon cosmesis and complication rates in patients being treated with definitive radiotherapy. However, cosmetic results remain satisfactory and complication rates are maintained at an acceptable level. Continued close follow-up will be required before definitive conclusions can be reached as to the overall incidence and severity of the changes noted.     

Radiation use and long-term survival in breast cancer patients with T1, T2 primary tumors and one to three positive axillary lymph nodes

BACKGROUND: For patients with Stage II breast cancer with one to three positive lymph nodes, controversy exists about whether radiation as a component of treatment provides a survival benefit. METHODS AND MATERIALS: We analyzed data from patients with Stage II breast cancer with one to three positive lymph nodes diagnosed from 1988-2002 in the Surveillance, Epidemiology, and End Results registry and compared the outcome of 12,693 patients treated with breast-conservation therapy with radiation (BCT + XRT) with the 18,902 patients treated with mastectomy without radiation (MRM w/o XRT). RESULTS: Patients treated with BCT + XRT were younger, were more likely to be treated in recent years of the study period, more commonly had T1 primary tumors, and had fewer involved nodes compared with those treated with MRM w/o XRT (p < 0.001 for all differences). The 15-year breast cancer-specific survival rate for the BCT + XRT group was 80% vs. 72% for the MRM w/o XRT group (p < 0.001). Cox regression analysis showed that MRM w/o XRT was associated with a hazard ratio for breast cancer death of 1.19 (p < 0.001) and for overall death of 1.25 (p < 0.001). The survival benefit in the BCT + XRT group was not limited to subgroups with high-risk disease features. CONCLUSIONS: Radiation use was independently associated with improved survival for patients with Stage II breast cancer with one to three positive lymph nodes. Because multivariate analyses of retrospective data cannot account for all potential biases, these data require confirmation in randomized clinical trials.     

Staging, therapy and prognosis of primary non-Hodgkin's lymphoma of bone and a comparison of results with localized Ewing's sarcoma: ten years experience at the Istituto Ortopedico Rizzoli

Thirty consecutive cases of localized primary non-Hodgkin's lymphoma of bone (PNHLB) were treated in a 10-year period at the Istituto Ortopedico Rizzoli with localized radiation (4 cases) and localized radiation and adjuvant chemotherapy (26 cases). The doses of radiation varied from 3000-4500 rad. A variety of staging procedures evolving with new diagnostic techniques over the 10 years were performed. Adjuvant chemotherapy comprised two different regimens of vincristine, adriamycin and cyclophosphamide. Twenty-four of the 26 patients (92%) have been free of disease with a median follow-up of 75.5 months (18-144 months). Two patients developed meningeal involvement and one patient, treated with radiation therapy only, developed a local recurrence. The results are compared to the management of 68 Ewing's sarcoma patients treated during the same period. Here, higher doses of localized radiation therapy (approximately 5000 rad) and similar adjuvant chemotherapy were administered. The survival was 32% (22/68) with a higher incidence of local recurrence (21%). These data indicate that PNHLB should be considered a separate entity from Ewing's sarcoma and can be treated successfully with lower doses of radiation to the primary tumor and adjuvant chemotherapy. The observations are also compared to a variety of other biological characteristics of Ewing's sarcoma. Since only two patients developed meningeal relapse, our experience does not permit a firm recommendation for routine prophylactic treatment of the central nervous system in PNHLB.     

Residual, unresectable, or recurrent colorectal cancer: external beam irradiation and intraoperative electron beam boost +/- resection

While combinations of external beam radiation (XRT) and surgery decrease pelvic recurrence and improve survival in the subgroups with residual disease (postop XRT) or initially unresectable disease (preop XRT), local recurrence is still unacceptably high, and survival could be improved. In view of this, pilot studies were instituted at Massachusetts General Hospital in which 32 patients received the standard previous treatment of external beam irradiation and surgery but in addition had an intraoperative electron beam boost of 1000-1500 rad to the remaining tumor or tumor bed. For the 16 patients who presented with unresectable primary lesions, the addition of intraoperative radiotherapy has resulted in a total absence of local recurrence with a minimum 20 month follow-up, and survival rates are statistically better than for the previous group treated with only external beam irradiation and surgical resection. In the group with residual disease, again there have not been any local recurrences in the 7 patients who received all treatment modalities versus 54% and 26% for the group with gross and microscopic residual treated with only external beam techniques. The remaining 9 patients presented with recurrent unresectable lesions--3 are alive (2 NED) at greater than or equal to 3 years.     

Endometrial adenocarcinoma: an analysis of treatment and outcome

This study aims to review the survival and morbidity in patients treated for endometrial cancer, at a single centre and analyses the effects of co-morbidity on these outcomes. Case notes of all patients referred to the Christie Hospital with endometrial carcinoma from January 1, 1993 to December 31, 1995 (n=499) were reviewed. Twenty patients presented with recurrence and were not included in this analysis. Three hundred and seventy-five patients had previously undergone a total abdominal hysterectomy and bilateral salpingoophorectomy (+/- pelvic lymphadenectomy). Of these, 175 received adjuvant external beam radiotherapy (XRT) only, 49 received XRT and brachytherapy, 30 received brachytherapy alone and 121 patients had no further therapy. One hundred and four patients were referred for primary treatment. Radical radiotherapy was administered to 63 patients who were unfit for surgery, with 10 of these receiving XRT + brachytherapy and 53 receiving brachytherapy alone. Thirteen patients received palliative XRT and 28 supportive care only. The overall 5-year survival for those treated radically was 73.3%. There was no significant survival difference between patients who underwent surgery and adjuvant radiotherapy, in whatever form (p=0.115). Patients who did not undergo surgery did less well as a group, although there was no significant survival difference between those treated with combination therapy or brachytherapy alone (p=0.33). Survival was significantly associated with FIGO stage, tumour grade, age (especially those >75 years) and co-morbidity (ACE-27 score). Late morbidity occurred in 46 patients, with severe toxicity affecting 12 (3.8%). Toxicity was associated with ACE-27 score (p=0.0019), treatment dose and modality, with 50% (n=6) of severe toxicity seen in patients receiving adjuvant XRT + ICT. These data demonstrate that survival in patients with endometrial carcinoma treated radically remains good, with the stage and grade of tumour being significant factors for overall survival. The incidence of severe morbidity related to radiotherapy of any modality was 3.8%. A high co-morbidity (ACE-27) score was significantly associated with poorer survival (p<0.0055) and increased late treatment morbidity (p=0.0019).     

Long-term results of combined modality therapy in primary bone lymphomas

Purpose: To report the Massachusetts General Hospital experience in the management of patients with primary bone lymphoma (PBL) treated with combined modality therapy (CMT).

Methods and Materials: Records from 37 eligible patients were reviewed. Two patients were treated with complete resection of the tumor, while 35 patients underwent radiation therapy with a median total dose of 54 Gy (range 38.35–66.5). All patients received combination chemotherapy, which contained doxorubicin in 33 cases. We compared the current data with our previous experience in patients treated with local measures only.

Results: Actuarial disease-free survival (DFS) at 5 and 10 years is 78% and 73%, respectively, while overall survival (OS) is 91% and 87%, respectively. No local failures were seen. Pathologic fracture at presentation influenced DFS (p = 0.005) and OS (p = 0.017) adversely. OS was compromised in patients older than 60 years (p = 0.059) and DFS in patients with pelvic primaries (p = 0.015). CMT was associated with improved DFS (p = 0.0008) and OS (p = 0.0001) compared to our historical controls. Ten patients (27%) developed complications requiring orthopedic procedures following completion of therapy at a median of 25.5 months (range 4–228).

Conclusion: Patients with PBL have a favorable outcome with CMT, which appears superior to radiation therapy alone. Late complications can be seen, especially in weight-bearing bones.     

Localized non-Hodgkin lymphoma involving the thyroid gland

BACKGROUND: The current study was undertaken to define the natural history and patterns of failure of localized non-Hodgkin lymphoma (NHL) involving the thyroid gland. METHODS: A retrospective review of 51 patients with Ann Arbor Stage I or II NHL involving the thyroid gland was performed. The median age of the patients was 59 years. There were 33 females. There were 21 patients with Stage I disease and 30 patients with Stage II disease. The International Prognostic Index (IPI) was known for 43 patients (it was 0 in 16 patients and > or = 1 in 27 patients). Fifteen patients had mediastinal involvement. Four patients underwent thyroidectomy, 18 patients received radiation therapy, 5 patients received chemotherapy, and 24 patients received combined modality therapy (CMT) with chemotherapy and radiation therapy. Treatment modality, patient gender, IPI, disease stage, and mediastinal involvement were examined for significance with regard to overall survival (OS) and failure free survival (FFS). RESULTS: The 5-year OS and FFS rates were 64% and 76%, respectively. The 5-year FFS rates by treatment regimen were 76% for radiation therapy, 50% for chemotherapy, and 91% for CMT (P = 0.15). IPI was found to be the only significant predictor of OS. The 5-year OS rates were 86% and 50%, respectively, for IPIs of 0 and > or = 1 (P = 0.02). None of the 5 variables were found to correlate significantly with FFS, although the 5-year FFS rates were 93% and 68%, respectively, for IPIs of 0 and > or = 1 (P = 0.08). Eleven patients failed treatment. Nine patients had a component of distant failure across the diaphragm. CONCLUSIONS: The prognosis of patients with localized NHL involving the thyroid gland appears to be very good, especially when CMT is used. Distant recurrences appear to account for the majority of treatment failures. The IPI was found to be a significant prognostic factor for OS and a marginal one for FFS.     

A phase II study of concurrent temozolomide and cis-retinoic acid with radiation for adult patients with newly diagnosed supratentorial glioblastoma

PURPOSE: This Phase II study was designed to determine the median survival time of adults with supratentorial glioblastoma treated with a combination of temozolomide (TMZ) and 13-cis-retinoic acid (cRA) given daily with conventional radiation therapy (XRT). METHODS AND MATERIALS: This was a single arm, open-labeled, Phase II study. Patients were treated with XRT in conjunction with cRA and TMZ. Both drugs were administered starting on Day 1 of XRT, and chemotherapy cycles continued after the completion of XRT to a maximum of 1 year. RESULTS: Sixty-one patients were enrolled in the study. Time to progression was known for 55 patients and 6 were censored. The estimated 6-month progression-free survival was 38% and the estimated 1-year progression-free survival was 15%. Median time to progression was estimated as 21 weeks. The estimated 1-year survival was 57%. The median survival was 57 weeks. CONCLUSIONS: The combined therapy was relatively well tolerated, but there was no survival advantage compared with historical studies using XRT either with adjuvant nitrosourea chemotherapy, with TMZ alone, or with the combination of TMZ and thalidomide. Based on this study, cRA does not seem to add a significant synergistic effect to TMZ and XRT.     

Treatment of localized aggressive lymphomas with combination chemotherapy followed by involved-field radiation therapy

Localized lymphomas of diffuse and aggressive histology sometimes undergo early hematogenous dissemination such that local therapies (surgery alone or followed by radiation therapy) are not curative in 100% of cases. We have treated 47 clinical stage I or IE patients with aggressive lymphoma histologies (diffuse large-cell, diffuse mixed, diffuse immunoblastic, follicular large-cell, diffuse small-non-cleaved cell) with four monthly cycles of an eight-drug combination chemotherapy program consisting of cyclophosphamide, etoposide, doxorubicin, nitrogen mustard (mechlorethamine), procarbazine, high-dose methotrexate with leucovorin rescue, and prednisone (Pro-MACE-MOPP) administered systemically followed by 40 Gy involved-field radiation therapy. Forty-five (96%) patients achieved a complete remission and no patient has relapsed with a median follow-up time of 42 months (range, 8 to 90). Both patients failing to achieve a complete remission died of lymphoma, and one patient died free of lymphoma 45 months after diagnosis during coronary artery bypass surgery unrelated to lymphoma or its treatment. Hospital admissions were necessary to manage complications on nine of 188 (5%) cycles of treatment. There were no treatment-related deaths. ProMACE-MOPP plus involved-field radiation therapy is safe and effective treatment for localized aggressive lymphoma.