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Biomedical subjects

M Gospodarowicz

Publications and source records attributed to M Gospodarowicz.

At least 19 recordsLinked to original sources
PubMed2003

Lung cancer after treatment for Hodgkin's disease: focus on radiation effects.

Aspects of radiation-induced lung cancer were evaluated in an international study of Hodgkin's disease. The study population consisted of 227 patients with lung cancer and 455 matched controls. Unique features included dose determinations to the specific location in the lung where each cancer developed and quantitative data on both chemotherapy and tobacco use obtained from medical records. The estimated excess relative risk (ERR) per Gy was 0.15 (95% CI: 0.06-0.39), and there was little evidence of departure from linearity even though lung doses for the majority of Hodgkin's disease patients treated with radiotherapy exceeded 30 Gy. The interaction of radiation and chemotherapy that included alkylating agents was almost exactly additive, and a multiplicative relationship could be rejected (P = 0.017). Conversely, the interaction of radiation and smoking was consistent with a multiplicative relationship, but not with an additive relationship (P < 0.001). The ERR/Gy for males was about four times that for females, although the difference was not statistically significant. There was little evidence of modification of the ERR/Gy by time since exposure (after a 5-year minimum latent period), age at exposure, or attained age. Because of the very high radiation doses received by Hodgkin's disease patients and the immunodeficiency inherent to this lymphoma and that associated with chemotherapy, generalizing these findings to other populations receiving considerably lower doses of radiation should be done cautiously.

Adult↗
PubMed2002

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

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

Adult↗
PubMed2001

A prospective study of factors predicting clinically occult spinal cord compression in patients with metastatic prostate carcinoma.

BACKGROUND: The objective of this study was to identify clinical parameters that predict occult subarachnoid space or spinal cord (SAS/SC) compression, as determined by magnetic resonance imaging (MRI), in patients with metastatic prostate carcinoma. METHODS: A prospective study was performed in which 68 patients with bone metastases from prostate carcinoma and a normal neurologic examination underwent MRI of the entire spine after documentation of clinical, X-ray, and bone scan parameters potentially predictive of occult SAS/SC compression. RESULTS: Occult SAS/SC compression was diagnosed in 22 patients (32%) using MRI. Nine patients (13%) had compressions at two discontinuous spinal levels. Extensive disease on bone scan, the duration of continuous hormonal therapy prior to study entry, and hemoglobin concentration were found to predict SAS/SC compression by univariate analysis. The extent of disease on bone scan and the duration of continuous hormonal therapy were independent predictors of SAS/SC compression by multivariate analysis (P = 0.02 and P = 0.04, respectively). The risk of occult SAS/SC compression increased from 32% to 44% in patients with a bone scan that showed > 20 metastases as the duration on hormones increased from 0 to 24 months. The risk in patients with fewer metastases increased from 11% to 17% over the same interval. The presence or absence of back pain was not predictive of SAS/SC compression. CONCLUSIONS: Patients who are at high risk for occult SAS/SC compression can be identified using clinical parameters and readily available diagnostic tests. These high-risk patients should undergo MRI screening with the aim of diagnosing and treating spinal cord compression before the development of neurologic deficits that may be irreversible.

Aged↗
PubMed2001

Adjuvant and salvage radiation therapy after radical prostatectomy for adenocarcinoma of the prostate.

PURPOSE: To evaluate the outcome of adjuvant and salvage radiotherapy (RT) after radical prostatectomy (RP) for clinically localized prostate cancer using conventional clinical end-points, and the biochemical relapse-free rate (bRFR). METHODS: Between 1987 and 1994, 113 node negative, hormonally naïve men received RT 1 month to 12 years after RP. Adjuvant RT was given for positive resection margins and/or pT3 disease. Salvage RT was given for a persistently elevated prostatic specific antigen (PSA), a rising PSA, or palpable recurrence post RP. Clinical and biochemical endpoints determined outcome. Log-rank testing and the Cox proportional hazards model identified factors predictive for biochemical relapse free rate. RESULTS: Median follow-up after RT was 3.7 years (range 0.2-9 years). Five-year clinical local control was 95% for patients with no palpable evidence of disease and 59% for those with palpable recurrence (P < 0.0001). 5-year bRFR was 81% for adjuvant RT, 19% for salvage of biochemical recurrence, 0% for patients with palpable disease (P < 0.0001). Improved bRFR for adjuvant and salvage RT was predicted by a Gleason score < 7 vs. 7 vs. > 7 (hazard ratio 1.53; 95% CI 0.99-2.35) and an undetectable pre-RT PSA vs. PSA < 2.0 ng/ml vs. PSA > 2.0 ng/ml (hazard ratio 3.81; 95% CI 2.47-5.87). Seminal vesicle involvement was not a statistically significant independent predictor of bRFR. CONCLUSIONS: The most favourable bRFR was observed for adjuvant therapy. Salvage was most successful with a pre-RT PSA < 2.0 ng/ml, or Gleason score < 7. Few patients with a pre-RT PSA > 2.0 ng/ml were salvaged, and none with palpable recurrence. These patients require investigation of alternative salvage strategies.

Adenocarcinoma↗
PubMed2001

Surveillance for stage I testicular seminoma. a review.

There is good evidence that patients with stage I seminoma can be managed equally well after orchidectomy with surveillance and adjuvant retroperitoneal radiation therapy. There is considerable reluctance amongst many physicians to accept surveillance as a management option in stage I seminoma and this is largely based on the excellent results achieved with adjuvant retroperiteonal radiation for many years. However, patients with stage I seminoma have a long life span and it is possible that the long-term sequelae of radiation treatment could have a negative impact on quality of life and longevity. It is of utmost importance to continue the study of the long-term effects of all current treatment approaches, in particular the risk of induction of second malignancies. However, the psychosocial impact on patients of surveillance and other management strategies must also be assessed. Stage I testicular seminoma is highly curable with currently available management approaches and the current challenge for clinicians is to maintain these excellent results while minimizing toxicity and individualising treatment to the specific social, economic and emotional circumstances of each patient. Surveillance should be one of the management options offered to patients with stage I seminoma.

Journal Article↗
PubMed2001

Does age influence the behaviour of localized prostate cancer?

OBJECTIVE: To assess, in a meta-analysis of published studies, whether age influences the behaviour of localized prostate cancer. METHODS: The Medline database was searched from 1966 to 2000 to identify studies analysing the outcome of localized prostate cancer by age, using disease-specific outcome measures, and having controlled for the established prognostic factors of grade, T stage and, where available, serum prostate-specific antigen (PSA) level. RESULTS: In all, 34 studies were identified, which included a total of 27 551 patients. The incomplete and heterogeneous nature of the reports precluded any quantitative overview. The findings of these reports are described and methodological shortcomings discussed. CONCLUSION: The evidence suggests that young age was an adverse prognostic factor in some series of radiation therapy before the advent of PSA assays, when men typically presented clinically with locally advanced disease, but that age has no significant prognostic effect in contemporary series of localized prostate cancer. Possible explanations for this difference are discussed, together with implications for further studies.

Age Factors↗
PubMed2001

Primary low-grade B-cell lymphoma of mucosa-associated lymphoid tissue type arising in the urinary bladder: report of 4 cases with molecular genetic analysis.

CONTEXT: Primary lymphoma of the urinary bladder is rare. Only 84 cases have been reported in the English literature to date, and none of these cases has had molecular confirmation of clonal immunoglobulin gene rearrangement. OBJECTIVES: To review all cases with primary urinary bladder lymphoma in our records, to classify them using the REAL classification, to confirm their immunophenotype and genotype, and to determine their outcome. DESIGN: We identified 4 cases of primary urinary bladder lymphoma in our medical records from a 30-year period. Immunohistochemical detection of immunoglobulin light chains and molecular analysis of immunoglobulin heavy-chain genes using the polymerase chain reaction were performed on paraffin-embedded material. RESULTS: All patients were older than 60 years. The male-female ratio was 1:3. All patients had a history of chronic cystitis. Histologic features of mucosa-associated lymphoid tissue lymphoma with centrocyte-like cells, plasmacytoid B cells, or both were observed in all cases. Monoclonality of B cells was demonstrated by immunohistochemistry, polymerase chain reaction, or both methods in every case. All patients presented with stage IAE disease, were treated with radiotherapy alone, and have been in continuous complete remission for 2 to 13 years. CONCLUSIONS: Primary bladder lymphomas are usually of low-grade mucosa-associated lymphoid tissue type. They are more common in females and are associated with a history of chronic cystitis. Lymphoepithelial lesions are seen only in association with areas of cystitis glandularis. B-cell clonality is readily demonstrable by immunohistochemistry and/or polymerase chain reaction analysis. Local radiotherapy appears to confer long-term control.

Aged↗
PubMed2000

Treatment-associated leukemia following testicular cancer.

BACKGROUND: Men with testicular cancer are at an increased risk of leukemia, but the relationship to prior treatments is not well characterized. The purpose of our study was to describe the risk of leukemia following radiotherapy and chemotherapy for testicular cancer. METHODS: Within a population-based cohort of 18 567 patients diagnosed with testicular cancer (from 1970 through 1993), a case-control study of leukemia was undertaken. Radiation dose to active bone marrow and type and cumulative amount of cytotoxic drugs were compared between 36 men who developed leukemia and 106 matched control patients without leukemia. Conditional logistic regression was used to estimate the relative risk of leukemia associated with specific treatments. All P values are two-sided. RESULTS: Radiotherapy (mean dose to active bone marrow, 12.6 Gy) without chemotherapy was associated with a threefold elevated risk of leukemia. Risk increased with increasing dose of radiation to active bone marrow (P for trend =.02), with patients receiving radiotherapy to the chest as well as to the abdominal/pelvic fields accounting for much of the risk at higher doses. Radiation dose to active bone marrow and the cumulative dose of cisplatin (P for trend =.001) were both predictive of excess leukemia risk in a model adjusted for all treatment variables. The estimated relative risk of leukemia at a cumulative dose of 650 mg cisplatin, which is commonly administered in current testicular cancer treatment regimens, was 3.2 (95% confidence interval = 1.5-8.4); larger doses (1000 mg) were linked with statistically significant sixfold increased risks. CONCLUSIONS: Past treatments for testicular cancer are associated with an increased risk of leukemia, with evidence for dose-response relationships for both radiotherapy and cisplatin-based chemotherapy. Statistically nonsignificant excesses are estimated for current radiotherapy regimens limited to the abdomen and pelvis: Among 10 000 patients given a treatment dose of 25 Gy and followed for 15 years, an excess of nine leukemias is predicted; cisplatin-based chemotherapy (dose, 650 mg) might result in 16 cases of leukemia. The survival advantage provided by current radiotherapy and chemotherapy regimens for testicular cancer far exceeds the small absolute risk of leukemia.

Adult↗
PubMed2000

Mucosa-associated lymphoid tissue lymphomas.

Mucosa-associated lymphoid tissue (MALT) lymphoma has attracted attention because its concept has amalgamated the study of etiology and pathogenesis in an intriguing group of lymphomas. MALT lymphomas are a B-cell malignancy with characteristic lymphoepithelial lesions; cells are CD20-positive and CD5- and CD10-negative. The molecular changes observed include trisomy 3, t(11;18), and t(1;14) translocations. They commonly occur in the stomach, orbit, salivary glands, and thyroid. Localized disease is present in 60% to 70% of patients. Involvement of multiple extranodal sites has been observed at presentation or during the course of disease. Lymphocyte homing has been implicated in gastrointestinal MALT and may be involved in other MALT lymphomas. Local therapy, either through surgery or radiotherapy, is curative in a high proportion of patients. MALT lymphomas respond to chemotherapy, but there is no evidence that cure can be achieved, although prolonged survival is common. Long-term follow-up is essential for study of the outcomes in this disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Second cancers among long-term survivors of Hodgkin's disease diagnosed in childhood and adolescence.

PURPOSE: To quantify the risk of second cancers among long-term survivors of Hodgkin's disease (HD) diagnosed before 21 years of age and to explore sex-, age-, and site-related differences. PATIENTS AND METHODS: We analyzed data from 5,925 pediatric HD patients, including 2,646 10-year and 755 20-year survivors, who were reported to 16 population-based cancer registries in North America and Europe between 1935 and 1994. RESULTS: A total of 157 solid tumors (observed/expected ratio [O/E] = 7.0; 95% confidence interval [CI], 5.9 to 8.2.) and 26 acute leukemias (O/E = 27.4; 95% CI, 17.9 to 40. 2) were reported. Risk of solid tumors remained significantly increased among 20-year survivors (O/E = 6.6, observed [O] = 40, cumulative risk = 6.5%) and persisted for 25 years (O/E = 4.6, O = 15, cumulative risk = 11.7%). Temporal trends for cancers of thyroid, female breast, bone/connective tissue, stomach, and esophagus were consistent with the late effects of radiotherapy. Greater than 50-fold increased risks were observed for tumors of the thyroid and respiratory tract (one lung and one pleura) among children treated before age 10. At older ages (10 to 16 years), the largest number of second cancers occurred in the digestive tract (O/E = 19.3) and breast (O/E = 22.9). Risk of solid tumors increased with decreasing age at HD on a relative but not absolute scale. CONCLUSION: Children and adolescents treated for HD experience significantly increased risks of second cancers at various sites for 2 to 3 decades. Although our results reflect the late effects of past therapeutic modalities, they underscore the importance of lifelong follow-up of pediatric HD patients given early, more aggressive treatments.

Adolescent↗
PubMed1999

Management of testicular seminoma.

Testicular seminoma is highly curable with currently available treatments. Today, there is good evidence that patients with Stage I disease can be treated equally well with either immediate adjuvant para-aortic and ipsilateral pelvic radiotherapy or close surveillance with treatment at the time of relapse. The decision as to which of these management strategies is adopted in an individual case is a complex function of physician preference, and the emotional, social, and economic circumstances of the patient. Ongoing research in Stage I seminoma is focused at reducing the side-effects of treatment either by modifying the radiation treatment plan or by using adjuvant chemotherapy in lieu of radiation. Stage II patients with small bulk retroperitoneal lymphadenopathy have a high probability of long-term disease control with radiotherapy. Patients with bulky Stage II disease or Stage III disease should be treated with cisplatin-based chemotherapy.

Analysis of Variance↗
PubMed1999

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.

Bone Neoplasms↗
PubMed1999

Lymphoma of the gastrointestinal tract.

Non-Hodgkin's lymphoma (NHL) of the gastrointestinal (GI) tract accounts for 4% to 20% of all NHLs and is the most common extranodal site of presentation. The stomach is the major organ involved by GI lymphoma. Helicobacter pylori infection, immunosuppression after solid-organ transplantation, celiac disease, inflammatory bowel disease, and human immunodeficiency virus (HIV) infection may be risk factors for GI lymphoma. A significant proportion of gastric lymphomas are of low-grade histology and arise from mucosal-associated lymphoid tissue (MALT). Such MALT lymphomas may be associated with H. pylori infection and may undergo complete regression following eradication of H. pylori. Lymphoma of the small bowel, colon, and rectum may also occur, but are less common than gastric lymphoma. Distinct clinicopathologic entities, such as primary intestinal T-cell lymphoma, immunoproliferative small intestinal disease, and multiple lymphomatous polyposis have been described. Surgery, radiation therapy, and chemotherapy have been used in the treatment of GI lymphomas. However, the optimal management of these lymphomas has never been determined by prospective randomized clinical trials. Such trials by cooperative groups are needed to answer many of the vital unanswered questions concerning extranodal lymphomas of the GI tract.

Gastrointestinal Neoplasms↗
PubMed1998

Magnetic resonance imaging (MRI) for localization of the prostatic apex: comparison to computed tomography (CT) and urethrography.

BACKGROUND AND PURPOSE: It is necessary to include the entire prostate in the high dose treatment volume when planning radical radiation for patients with prostate cancer. We prospectively compared magnetic resonance imaging (MRI) to computed tomography (CT) and urethrography as means of localizing the prostatic apex. MATERIALS AND METHODS: Thirty patients with clinically localized prostate cancer had a sagittal T2-weighted MRI scan and a conventional axial CT scan performed in the treatment position prior to the start of radiotherapy. Twenty of these patients had a static retrograde urethrogram performed at simulation. The position of the MRI and CT apices were localized independently by two radiation oncologists. In addition, the MRI apex was localized independently by a diagnostic radiologist. The urethrogram apex, defined as the tip of the urethral contrast cone, was easily identified and was therefore localized by only one observer. RESULTS: There was good interobserver agreement in the position of the MRI apex. Interobserver agreement was significantly better with MRI than with CT. There were no systematic differences in the position of the MRI and CT apices. However, the MRI apex was located significantly above and behind the urethrogram apex. There was poor correlation between MRI and CT and between MRI and urethrogram in the height of the apex above the ischial tuberosities. There was 83% agreement between MRI and CT and 80% agreement between MRI and urethrogram in the identification of patients with a low-lying apex. The apex, as determined by MRI, was <2 cm above the ischial tuberosities and therefore potentially under-treated in 17% of the patients. CONCLUSIONS: MRI is superior to CT and urethrography for localization of the prostatic apex. All patients undergoing radiotherapy for prostate cancer should have localization of the apex using MRI or a technique of equal precision to assure adequate dose delivery to the entire prostate and to minimize the unnecessary irradiation of normal tissues.

Adenocarcinoma↗
PubMed1998

Management of stage II seminoma.

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

Adult↗
PubMed1998

Cancer staging.

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Academies and Institutes↗