Immuno-chemotherapy in metastatic renal cell carcinoma: long-term results from the rambam and linn medical centers, Haifa, Israel.

Nephrectomy, immuno-chemotherapy and resection of residual disease have been the treatment of choice for patients with metastatic renal cell carcinoma during the past decades. The aim of this study was to report the long-term results of this treatment approach. Sixty-two patients with metastatic renal cell carcinoma participated in a Phase II study. At diagnosis, 32 patients had localized disease, 30 had metastatic disease and 53 underwent nephrectomy. Metastatic sites were lungs, lymph nodes, bones and liver. Immuno-chemotherapy consisted of: interleukin-2, interferon alpha, 5-fluorouracil and vinblastine. All patients were evaluated for toxicity and response to treatment. CR was achieved in 4 patients and PR in 14. Seven patients, with maximum response to immuno-chemotherapy underwent resection of residual tumor and reached CR. Therefore, CR was achieved in 11 patients (18%) with a median survival of +67 months. Flu-like symptoms were the common side effects. Performance status and histology type significantly affected survival. Nephrectomy, immuno-chemotherapy and resection of residual disease are recommended for patients with metastatic renal cell carcinoma.

Second primary tumors in mycosis fungoides patients: experience at the Northern Israel Oncology Center (1979-2002).

PURPOSE: Mycosis fungoides (MF) patients enjoy longstanding remissions following total skin electron irradiation (TSEI) but run the risk of developing secondary malignancies. Our purpose was to report our experience with the phenomenon of secondary malignancies in MF patients. PATIENTS AND METHODS: From 1979 to 2002, 84 patients with biopsy-proven MF were referred to our department for TSEI, using the modified Christie Hospital translational technique until 1992 and the Stanford technique after 1992. Median total dose was 32 Gy (range 16-44) Christie; 30 Gy (range 15-36) Stanford. Underdosed areas were boosted with a median total dose of 10-20 Gy. RESULTS: During a median follow-up of 73 months (range 2-191) from the end of the TSEI, 12 (15%) patients developed 17 second primary tumors within the irradiated areas and 6 patients developed 7 second primary tumors, either simultaneously with the newly diagnosed MF or prior to introduction of radiation therapy. CONCLUSION: The long-term prognosis was related solely to the second primary. Due to excellent long-lasting response rates following TSEI coupled with long-term survival, and the prognosis mainly associated to the stage and histology of the second malignancy, physicians should be aware of the possibility of second primary tumors.

Primary lymphoma of the liver: clinical features and outcome of 9 patients.

PURPOSE: Primary liver lymphoma (PLL) is a rare lymphoproliferative disorder of unknown etiology. The prognosis in affected patients is poor, consisting of brief remissions, rapidly developing resistance to chemotherapy, early recurrence, and short survival. Most studies related to PLL are based on case reports. The aim of this retrospective study was to review our experience with PLL. PATIENTS AND METHODS: From 1985 to 2000, 9 patients who fulfilled the diagnostic criteria for PLL were treated at our hospital. All patients underwent a thorough work-up and were staged accordingly. RESULTS: The disease occured in middle and higher-aged patients (median age 63 years). Primary presenting complaints were abdominal pain, mainly in the right upper quadrant, and hepatomegaly. Liver function tests and lactate dehydrogenase (LDH) levels were elevated. Liver imaging (computed tomography-CT) and isotopic methods (gallium scan) demonstrated liver involvement either as solitary or multiple space-occupying lesions. Pathologic examination demonstrated diffuse, large cell (DLCL), B-type lymphoma in 7/9 (78%) patients. Doxorubicin-based chemotherapy was the mainstay of treatment. Good partial or complete remission rates were achieved in 7 patients, albeit for a brief period of time. CONCLUSION: Most patients with PLL succumb to their illness, despite its being relatively chemotherapy-sensitive. The introduction of intensive chemotherapy, plus/minus radiotherapy, and/or surgery has been considered in some studies.

Methylprednisolone as antiemetic treatment in breast-cancer patients receiving cyclophosphamide, methotrexate, and 5-fluorouracil: a prospective, crossover, randomized blind study comparing two different dose schedules.

The antiemetic response and side effects resulting from treatment with methylprednisolone (MPA) given on two different dose schedules were evaluated in 20 women with breast cancer who were undergoing chemotherapy consisting of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). This randomized, crossover, double-blind study compared the antiemetic efficacy of a single dose of 125 mg MPN with that of two such doses. The study demonstrated the superiority of the latter protocol in preventing CMF-induced nausea and vomiting. The rate of antiemetic response to single vs double doses was as to follows: complete protection, 17% vs 30%; partial and minimal protection, 39% vs 55%; and no protection, 44% vs 15% of the courses, respectively (P = 0.0087). No difference in the antiemetic response rate was found between the first and the second course. Treatment with MPN was well tolerated, and no difference in the incidence of side effects was found between the single-dose and the double-dose schedule. We recommend the use of two doses of 125 mg MPN as prophylactic antiemetic treatment in breast-cancer patients receiving CMF chemotherapy.

Adriamycin, vinblastine and mitomycin C as second-line chemotherapy in advanced breast cancer.

Thirty-six evaluable patients with metastatic measurable breast carcinoma previously treated with CMF or CMFVP were given second-line chemotherapy with Adriamycin, vinblastine, and mitomycin C (AVM), as follows: Adriamycin 20 mg/m2 and vinblastine 6 mg/m2 by i. v. push on days 1, 8, and 15, and mitomycin C 10 mg/m2 i. v. on day 1, every 6 weeks. Ten patients (28%) achieved partial remission (PR) lasting a median of 10 months, and eight patients (22%) experienced improvement of a lesser level than PR. An additional nine patients (25%) had disease stabilization; in the remaining nine patients (25%), persistent disease progression was observed. The median survival from the onset of AVM was 7 months for all patients; patients with PR survived a median of 13 months. Myelotoxicity was substantial and frequently interfered with the optimal administration of AVM, especially in patients with skeletal metastases; four patients were hospitalized with leukopenia and fever; all recovered promptly; one death was probably related to thrombocytopenia and CNS bleeding. Our results with AVM are similar to the average response rate published in the literature with the use of Adriamycin as a single agent in previously treated patients with advanced breast cancer.

Primary lymphoma of the parotid gland: a report of twelve cases with a review of the literature.

Primary extranodal lymphoma of the salivary gland is an extremely rare disease. In this report we describe twelve cases of primary lymphoma of the parotid gland seen at a single centre, and review the relevant literature. The 12 cases were treated in different departments and did not receive a uniform therapeutic approach. All three patients with Hodgkin's disease are still alive and two are in complete remission after initial radiotherapy. One of these cases developed stage 4 disease and had to receive combination chemotherapy subsequently. Of the 9 non-Hodgkin's lymphoma (NHL) patients, four had low grade NHL and 5 intermediate or high grade NHL. Of these, 2 died with disseminated disease. However, 6 are still alive and well from 1 to 5 years after therapy. These cases were treated with surgery alone, radiotherapy alone or combination chemotherapy with an anthracycline-bearing regimen. Consequently, we are unable to draw any conclusions relating the success of therapy in these cases, nor can we suggest therapeutic guidelines on the basis of this study alone. The treatment of parotid lymphoma is discussed briefly in the light of the available literature. In most cases, symptoms related to an enlarging mass in the parotid region, were evident. In the light of the above data, we suggest that, despite its rarity, lymphoma of the salivary gland should always be considered in the differential diagnosis of a parotid mass. No correlation between lymphoma and Sjogren's syndrome was noted in the present study.

The effect of low-dose interleukin-2-based immunotherapy on salivary function and composition in patients with metastatic renal cell carcinoma.

One of the side-effects accompanying low-dose recombinant interleukin-2 (rIL-2)-based immunotherapy is salivary hypofunction. We evaluated the functional and compositional whole salivary profile at both resting and stimulated conditions in 10 renal cell carcinoma patients who received prolonged low-dose rIL-2-based immunotherapy. Following the termination of 4 weeks of the combined administration of rIL-2 and recombinant interferon-alpha (rIFN-alpha), we found significant reductions of salivary flow rates at resting condition, accompanied by significant multiple compositional alterations, including increases in calcium, magnesium and phosphate concentrations, and significant reductions in total protein concentration. In contrast, no flow rate reduction was noted under stimulated condition, and the only significant altered compositional component was the phosphate. We recommend salivary-supporting therapies and anticariogenic treatments for patients undergoing low-dose rIL-2-based immunotherapy.

Growth rate analysis of lung metastases appearing 18 years after resection of cutaneous adenoid cystic carcinoma. Case report and review of the literature.

Growth rate analysis of lung metastases of a cutaneous adenoid cystic carcinoma, which appeared 18 years after the resection of the primary tumor from the scalp is presented. The doubling times of the metastases were long compared with that of other lung metastases. They were 22 months for the metastasis in the right lung and 70 months for the metastasis in the left lung, with a shortening of the doubling time in the left side to 10.4 months in the last 4 months of observation. Backward extrapolation showed that the metastases to the lung were disseminated before the diagnosis and surgical resection of the primary tumor. To our knowledge, this is the third reported case of lung metastases from a cutaneous adenoid cystic carcinoma out of 25 documented cases. We present a review of the literature and discuss the clinical implications of our findings.

Acute pericarditis following bleomycin: a case report and literature analysis.

Acute pericarditis following bleomycin treatment is extremely rare. A case report and analysis of the literature are presented.

Malignant pericardial effusion associated with metastatic rectal cancer: case report.

Pericardial effusion caused by malignant disease is an uncommon disorder. We present a patient with rectal cancer who developed malignant pericardial effusion as the main site of relapse 18 months following surgery. We discuss the incidence and the therapy of this condition.

Methylprednisolone versus metoclopramide as antiemetic treatment in patients receiving adjuvant cyclophosphamide, methotrexate, 5-fluorouracil (CMF) chemotherapy: a randomized crossover blind study.

Nineteen women receiving their first cycle of adjuvant chemotherapy for early breast cancer were randomized between two antiemetic drugs: methylprednisolone (MPN) 125mg and metoclopramide (MCP) 20mg, both given by intravenous push as a single dose. The chemotherapy included: cyclophosphamide, methotrexate and 5-fluorouracil (CMF). The total response rates for MPN and MCP were: complete protection 11% versus 0% and partial protection 63% versus 11% of the patients, respectively (P = 0.007). Eighteen patients (95%) preferred MPN over MCP. Common side effects with both drugs were: drowsiness, headache and diarrhea. MPN is recommended as an antiemetic in patients receiving CMF adjuvant chemotherapy.

Methylprednisolone and chlorpromazine in patients receiving cancer chemotherapy: a prospective non-randomized study.

Seventy-six consecutive patients receiving chemotherapy were evaluated for the antiemetic efficacy and side-effects of the combination of chlorpromazine (CPM) and methylprednisolone (MPN). All patients had previously received the same chemotherapy with metoclopramide in conventional dosage and experienced severe emesis. A significant antiemetic response was achieved in 70% of the patients, and in 28% of them the antiemetic protection was complete. The most common side effects were drowsiness, dry mouth and headache. The combination of CPM and MPN is effective, well tolerated and is recommended for outpatients receiving chemotherapy for cancer.

Implementing a tantalum wire mesh to increase the skin dose in low-energy electron irradiation of the chest wall.

Radiation treatment of the post-mastectomy chest wall is performed in our institution by straight-on electron irradiation. The chest-wall thickness is measured and the beam energy is chosen so that the chest wall is treated to therapeutic doses, while sparing the underlying lung tissue. The most commonly chosen energies are 6 and 9 MeV. The skin dose should be 90% of the dose prescribed to the chest wall, which is higher than can be achieved with 6- and 9-MeV beams because of the low surface dose. The addition of a bolus slab during part of the treatment can correct for this; however, the added depth means that a higher energy has to be chosen, which will increase the lung dose (the higher the electron energy, the slower the falloff of the electron depth-dose curve). A mesh of a high-Z material above the skin gives rise to obliquely scattered and low-energy electrons that effectively spoil the buildup zone. Dosimetric measurements of a Tantalum (Ta) mesh were performed using a dose scanner in a water tank and a film inserted in a humanoid phantom during a simulated treatment. Measurements were also done for the clinically relevant cases of oblique beam incidence and with the mesh placed 1 cm above the surface. The measurements demonstrate the spoiling of the buildup zone, while having only a moderate influence on the dose distribution beyond the dose maximum. The mesh also changes the absolute dose. In a fractionated regime, the first part of the treatment would be without the mesh, adding it only during the latter fractions. The total dose distribution gives 90% to the skin, while leaving the depth-dose characteristics beyond the dose maximum virtually unchanged.

Dose perturbation due to the presence of a prostatic urethral stent in patients receiving pelvic radiotherapy: an in vitro study.

Temporary metallic intraprostatic stent is a new alternative treatment for patients with urinary obstructive syndrome caused by prostate cancer. Definitive radiotherapy is a treatment of choice for localized prostate cancer. This study evaluates in vitro the effect of a urethral intraprostatic metallic stent on the dose absorbed by the surrounding tissue. The study was designed to mimic the conditions under which the prostatic stent is placed in the body during pelvic irradiation. A urethral stent composed of a 50% nickel-50% titanium alloy (Uracoil-InStent) was imbedded in material mimicking normal tissue (bolus) at a simulated body depth of 10 cm. The distribution of the absorbed dose of irradiation was determined by film dosimetry using Kodak X-Omat V film. Irradiation was done in a single field at the isocenter of a 6 MV linear accelerator with a field size of 7 x 7 cm. The degree of film blackening was in direct proportion to the absorbed dose. The measurements showed an increase in dose of up to 20% immediately before the stent and a decrease of up to 18% immediately after the stent. These changes occurred within a range of 1-3 mm from both sides of the stent. In practice, irradiation in prostate cancer is given by two pairs of opposed co-axial fields; a total of four fields (Box Technique). The dose perturbations are partly cancelled in a pair of opposed beams resulting in a net variation of +/- 4%; therefore, the presence of the intraprostatic stent should not influence radiotherapy planning for prostate cancer.

[Prostatic specific antigen for detection and monitoring of prostatic cancer].

Prostatic specific antigen (PSA) can be detected in normal and benign hypertrophic prostates, as well as in prostatic cancer and its metastases. Since it appears in the serum, this glycoprotein has become an established marker for the detection and monitoring of prostate cancer. Using a radioimmunoassay (CIS--Biointernational, France), we found serum PSA levels higher than 4 ng/ml in 55 of 58 patients with prostatic cancer. The concentrations were proportional to tumor stage: significantly higher in stages C and D than in stages A and B (p less than 0.002). In all 6 cases with occult prostatic carcinoma (stage A), levels were higher than 15 ng/ml. PSA was found to be a good indicator of response to therapy, as well as a marker of tumor progression during follow-up. After radical prostatectomy serum PSA levels decreased to below 1 ng/ml. Following radiotherapy levels returned to normal within 1-6 months in 8 of 11 patients. In 21 of 23 with metastases serum PSA decreased during hormonal treatment. In 3 who responded initially to hormonal therapy, levels increased before clinical manifestation of tumor progression. We conclude that PSA is a sensitive serum marker for the diagnosis of prostatic cancer in cases of metastatic disease of unknown origin, as well as for monitoring the response to treatment of prostatic carcinoma. The use of PSA serum levels for screening for prostatic cancer is still controversial.

[Radiotherapy of localized prostatic carcinoma].

112 patients with localized prostate cancer, clinical stage A2-C, were treated by definitive radiotherapy between 1982-1988. Radiation volume encompassed the prostate, seminal vesicles and pelvic lymph nodes. The 10-year actuarial survival figures were: overall 51%; stage A2 87%; stage B 50%; stage C 36%; well differential tumors 67%; moderately differentiated 50%; poorly differentiated 32%; patients with local tumor control 55%; and patients with minimal local control 36%. It is concluded that external beam irradiation is effective in localized prostatic cancer. Stage and grade are prognosticators of survival.

Diagnosis and treatment of primary non-Hodgkin's lymphoma of the parotid gland: a retrospective study - Experience at the Northern Israel Oncology Center (1977-1999).

PURPOSE: The treatment and outcome of primary parotid gland non-Hodgkin's lymphoma (PGL) has rarely been described. This retrospective study documents the clinicopathologic features and treatment results in this relatively rare entity. PATIENTS AND METHODS: This study was conducted on 11 patients diagnosed and treated for primary PGL over a period of 22 years. RESULTS: Of the 4 male and 7 female patients, only one presented with the classic pattern of Sjögren's syndrome (SS) simultaneous with PGL, and only 4 patients demonstrated a low-grade Maltoma type. None of the patients had evidence of disease at the end of the primary treatment; 4 patients are alive and well from 6 months to 10 years after the end of treatment. Four patients relapsed and died due to therapy-resistant disease and 3 patients died of nonmalignant causes while in complete remission. CONCLUSION: The majority of patients with primary non- Hodgkin's lymphoma of the parotid gland present with early- stage disease. Accurate staging is mandatory. Low-grade, localized PGL can be treated successfully with primary radiotherapy alone. The aggressive type of PGL should be treated with combined chemoradiotherapy-based regimens.

[Value of positron emission tomography and computer tomography (PET/CT) for urologic malignancies]. / Intérêt de la tomographie par émission de positons couplée à la scanographie (TEP/TDM) dans les cancers urologiques.

Positron emission tomography is a functional imaging technique that allows the detection of the regional metabolic rate, and is often coupled with other morphological imaging technique such as computed tomography. The rationale for its use is based on the clearly demonstrated fact that functional changes in tumor processes happen before morphological changes. Its introduction to the clinical practice added a new dimension in conventional imaging techniques. This review presents the current and proposed indications of the use of positron emission/computed tomography for prostate, bladder and testes, and the potential role of this exam in radiotherapy planning.