[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.

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.

Topical superoxide dismutase reduces post-irradiation breast cancer fibrosis.

Fibrosis following breast radiotherapy for mammary cancer is a frequent undesired effect with objective (esthetic) and subjective (pain) consequences. Forty-four patients with clinical radiofibrosis following conservative treatment of breast cancer were evaluated for the local antifibrosis effect of copper zinc superoxide dismutase [SOD(Cu/Zn)]. Extracted SOD(Cu/Zn) in a concentration of 3,600 units/mg was applied as ointment to the fibrotic affected area, b.i.d. for 90 days, in a total dose of 40 mg. The radiofibrosis intensity was scored on the basis of clinical criteria (pain and the fibrosis area) before and after SOD(Cu/Zn) treatment. SOD(Cu/Zn) was found to be effective in reducing radiation induced fibrosis by a lowering pain score in 36/39 patients and a decrease of the fibrotic area size in half cases, after 6 months. The intensity and changes of breast fibrosis were assessed also by mammography and, for the topographical distribution of subcutaneous temperature, by infrared thermography. Mammography density suggested decreased fibrosis in one third of patients. Thermography showed that fibrosis was accompanied by two zones clinically indistinctive: a central area with maximum thermal activity, called "Maximal Thermic zone" (MTZ) and a peripheral area with less thermal activity but higher than in the surrounding normal tissue, "Transitional Thermic Zone" (TTZ). Both MTZ and TTZ were significantly decreased in 36/44 patients after SOD(Cu/Zn) treatment. Clinical changes persisted all along the study. Treatment was well tolerated except for one case of local allergic reaction, and no important side effects. Molecular mechanisms involved are discussed. Further studies are running to confirm and explain these results.

Targeting pulmonary metastases of renal cell carcinoma by inhalation of interleukin-2.

INTRODUCTION: Pulmonary metastases of renal cell carcinoma (RCC) are associated with poor prognosis. Inhalation therapy with interleukin-2 (IL-2) is thus an appealing method for palliation. This multicenter study summarizes the national experience of IL-2 inhalation in patients with lung metastases of RCC. PATIENTS AND METHODS: Forty patients (median, 66.5 years of age) with radiologically documented progressing pulmonary metastases were enrolled. All patients had to be able to comply with inhalation technique, and were not candidates for other treatment options. Twenty-eight patients were systemic treatment-naïve. The protocol included three daily inhalations of IL-2 to a total dose of 18 MU. Treatment had to be continued until one of the following occurred: progression; a complete response; a life threatening toxicity; or patient refusal. Response was assessed using the Response Evaluation Criteria in Solid Tumors (RECIST) system. RESULTS: The disease-control rate reached 57.5%, with a partial response rate of 2.5% and a disease stabilization rate of 55%. Median time to progression was 8.7 months. The main side-effects were cough and weakness. CONCLUSIONS: Inhalation of IL-2 for the treatment of pulmonary metastases in RCC is feasible, tolerable and beneficial in controlling progressive disease for considerable periods of time. The definition of response of biological therapy may need to be re-assessed and modified: stable disease should be regarded as a favorable response.

Primary lymphoma of bone--a retrospective study. Experience at the Northern Israel Oncology Center (1979-2000).

OBJECTIVE: This retrospective study describes our experience with the diagnosis, treatment, results and long-term follow-up of primary bone lymphoma (PBL). PATIENTS AND METHODS: Nineteen patients diagnosed with PBL were reviewed. Seven patients presented with stage I(E) disease, four with stage II(E) (regional lymphadenopathy), and eight with stage IV disease (disseminated bone involvement). Only one stage IV patient exhibited 'B' symptoms. The majority (72%) demonstrated diffuse, large cell, B-type lymphoma. All patients were treated with adriamycin-based chemotherapy and consolidation radiotherapy to the primary site (8 patients: early PBL) or the most bulky area (3 patients: stage IV PBL). RESULTS: Ten stage I(E)/II(E) patients are alive with no evidence of disease (NED) and only one died due to metastatic secondary lung cancer while with NED from his PBL. Eight stage IV patients are alive with NED. Median follow-up for all living patients: 77 months. Side effects were mild and did not necessitate delay in treatment. CONCLUSIONS: Our departmental policy of treating PBL patients with an anthracycline-based regimen and involved field radiotherapy proved to be successful in achieving excellent long-term, disease-free survival. Phase III randomized, controlled, clinical trials will determine the true role of consolidation radiotherapy in PBL, when considering severe late side effects, including radiation-induced bone tumors.

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.

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.

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.

Octreotide in the treatment of severe chemotherapy-induced diarrhea.

BACKGROUND: Chemotherapy-induced diarrhea (CID) is a common side effect of a number of chemotherapeutic agents. Conventional therapy for severe CID with opioids or loperamide is moderately effective. A prospective trial was conducted using octreotide acetate for treatment of severe CID refractory to loperamide. PATIENTS AND METHODS: Thirty-two patients with grade 2 and 3 CID refractory to loperamide were treated with octreotide at a dosage of 100 microg subcutaneously 3x/day for three days followed by 50 microg 3x/day for three days. Previous chemotherapy consisted of regimens containing fluorouracil, leucovorin, CPT-11, cyclophosphamide, methotrexate and cisplatin. Primary tumors were colorectal (n = 23), gastric (n = 3), and other cancers (n = 6). RESULTS: Complete resolution of diarrhea was obtained in 30 of 32 patients (94%); 5 within 24 hours, 14 within 48 hours, and 11 within 72 hours of treatment. Nineteen patients were treated as outpatients. Thirteen were hospitalized for a median of three days. Response was unaffected by age, gender, performance status, previous chemotherapy or primary tumor site. No side effects related to octreotide were observed. CONCLUSIONS: Octreotide 100 microg subcutaneously 3x/day for three days is an effective, safe treatment for CID given primarily or as a second-line therapy after loperamide failure.

T-cell subpopulation in patients with metastatic renal cell carcinoma treated by recombinant interleukin-2, recombinant interferon-alpha, 5-fluorouracil, and vinblastine.

T-cell subpopulations were evaluated in 10 patients with metastatic renal cell carcinoma treated with recombinant interleukin-2, recombinant interferon-alpha, 5-fluorouracil, and vinblastine. T-cell subpopulation was tested by flow cytometry, and the results were compared with healthy control subjects. Mean T-cell values before treatment as compared with control were as follows: CD3, 68 vs. 73%; CD4, 34 vs. 53%; CD8, 38 vs. 31%; CD4/CD8, 1.1 vs. 1.8; CD4CD69, 20 vs. 47%, and CD8CD69, 24 vs. 19%. The difference in CD4, CD4/CD8, and CD4CD69 was statistically significant. After treatment (8 weeks), the values of CD4/CD8 ratio and CD4CD69 increased. Three patients achieved complete response, two partial response, and two had stabilization of the disease. After treatment, the CD4/CD8 ratio increased in complete responders, from 1.1 to 2.0, and CD4CD69 increased in complete and partial responders, from 11 to 37% and 23 to 31%, respectively. In nonresponders, no similar change was observed. In conclusion, increases in CD4/CD8 ratio and CD4CD69 levels in metastatic renal cell carcinoma patients may be associated with response to immunochemotherapy.

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.

[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.

Megestrol acetate in advanced breast carcinoma after failure to tamoxifen and/or aminoglutethimide.

Seventy-three patients with metastatic breast cancer, whose disease progressed on hormonal therapy with tamoxifen or aminoglutethimide, were treated with megestrol acetate, 160 mg/day. No complete responses were observed. Partial response was achieved in 3 patients (4%), for a median of 9 months (range 5-13). Thirty-five patients (48%) remained stable, for a median of 8 months (3-26). The remaining 35 patients (48%) had clear progression of their metastatic disease on therapy. Response to megestrol acetate was achieved in patients with metastases in bone and pleura only. There was no correlation between response to megestrol acetate and response to prior chemotherapy, prior tamoxifen therapy, previous treatment with aminoglutethimide, or hormone receptor status. The actuarial 24-month survival for all patients was 37%. The main side effects of megestrol acetate included weight gain (20% or over), pruritus, elevation of blood pressure, weakness, and vaginal bleeding; they were only occasionally observed. The objective improvement observed during this trial is disappointing; the only reasons to justify the use of megestrol acetate as second- or third-line hormonal therapy in patients with metastatic breast cancer, would be the relatively long duration of disease stabilization in a large proportion of patients, and the low toxicity observed with the drug.

Surveillance in patients with stage I testicular nonseminomatous germ cell tumors.

Fourteen patients with testicular nonseminomatous germ cell tumor, clinical stage I were entered into a surveillance study. Median age was 31 (range 18-58). Three patients had pure tumor, and 11, mixed tumor. In 2 patients, vascular invasion was noted, and in 1, involvement of the spermatic cord. Serum alpha fetoprotein and beta subunit choriogonadotropin were high in 9 and in 3 patients, respectively. In median follow-up of 21 months (range 2-63), 3 patients relapsed: 1 had inguinal lymphadenopathy and 2 had lung metastases at 12, 4, and 16 months, respectively. Salvage chemotherapy PEB and PVB achieved complete response in the latter 2 patients for 6 and 49 months. Except for 1 patient lost to follow-up, all are alive.

[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.

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.