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.

Vinorelbine/VP-16 (etoposide) in metastatic breast cancer: a phase II study.

PURPOSE: This phase II study was conducted to evaluate the efficacy and tolerability of vinorelbine (navelbine) and oral VP-16 (etoposide) in pretreated metastatic breast cancer (MBC) patients. PATIENTS AND METHODS: Twenty-two female patients with therapy-resistant metastatic breast cancer were treated with vinorelbine 25 mg/m(2) i.v. on days 1 and 8 and oral VP-16 50 mg/m(2)/day for 14 days. Cycles were repeated every 28 days. Treatment was given until clear evidence of disease progression. RESULTS: Complete remission was observed in 3 (14%) patients, and partial remission or stable disease in 10 (45%) patients. Median duration of response was 4 months (range 2-8). Symptomatic improvement, irrespective of imaging methods results, as evaluated through improved performance status (PS), the lack of requirement for urgent palliative radiotherapy, and a decrease in steroids and analgesics doses was demonstrated in 10 (45%) patients through a special questionnaire completed by all patients. Side effects were manageable. Dose modification due to leucopenic fever were necessary in only 3 patients. Previous radiation therapy did not mitigate the application of full doses of chemotherapy. CONCLUSION: Vinorelbine/VP-16 combination is active and tolerable in relapsed and heavily pretreated MBC patients.

Long-standing complete remission following mitomycin-C/vinblastine chemotherapy for cutaneous and lymph node metastases from breast cancer resistant to multiple chemotherapy and hormonal lines and extensive radiotherapy: an unusual case.

Widespread cutaneous and lymph nodes recurrence in breast cancer is regarded as therapy-resistant disease. We describe a 50-year-old patient who presented with treatment-refractory disease following multiple lines of chemo- and hormonotherapy, photodynamic therapy and radiotherapy, including re-irradiation to extended volumes of her chest, upper abdomen, back and regional lymph nodes. Following treatment with mitomycin-C (MMC)/vinblastine (VLB) alone, she entered sustained complete remission of 1-year duration without any side effects. A brief review of the current literature is also presented. The MMC/VLB combination might achieve reasonable response and improvement of quality life even in patients with advanced breast cancer.

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.

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.

Trauma as an etiologic factor of primary bone lymphoma: a report of 4 cases.

Primary bone lymphoma (PBL) is a rare entity. Nevertheless, very high long-term complete remission and survival rates following adriamycin-based chemotherapy alone or combined with involved-field radiation therapy have been reported. While the etiology is unknown, factors comprising local or general immunocompromised states have been suggested. Sporadic cases of local trauma followed by the emergence of primary bone lymphoma have been described. We describe 4 patients who developed primary bone lymphoma following direct trauma to a specific bone area. All 4 are alive with no evidence of disease after being treated with a combined chemo-radiotherapy regimen.

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.

Consolidation radiation therapy following cytoreductive surgery, chemotherapy and second-look laparotomy for epithelial ovarian carcinoma: long-term follow-up.

BACKGROUND: From 1979-1987, 139 stage IC-IV ovarian cancer patients who had undergone cytoreductive surgery received 6-11 cycles of cisplatin and adriamycin. STUDY DESIGN: Eighty-four clinically complete responders underwent second-look laparotomy, and 60 of them received consolidation abdominal irradiation. The patients were then followed for a median follow-up of 39 months. RESULTS: Five- and 10-year actuarial survival for all patients was 43% and 24%, for no residuum at primary surgery, 80% and 35%, for residual tumor <2 cm, 45% and 35%, and for residual tumor >2 cm, 20% and 4%. Median survival for stage III-IV patients negative at second-look laparotomy was 72 months in irradiated compared to 25 months in non-irradiated patients (P = 0.14) and 77 months in irradiated patients with microscopic disease at second-look laparotomy. Median survival in patients with macroscopic disease at second-look laparotomy was 23.5 months if irradiated compared to 18 months if not (P = 0.05). CONCLUSIONS: Consolidation whole abdominal irradiation in advanced stages of ovarian cancer may be of value in patients with negative or microscopic disease at second-look laparotomy. Unfortunately, despite the initial survival advantage observed in irradiated patients, owing to late recurrences there was no significant difference in their long-term survival probability.

Primary malignant lymphoma of the parotid gland report of three cases.

AIMS AND BACKGROUND: To document the clinicopathologic features and treatment modalities of primary malignant parotid gland lymphoma, based on three cases diagnosed and treated at Oldchurch Hospital, Romford, UK. METHODS: Three patients, two with stage II and one with stage IV disease, received primary treatment consisting of chemotherapy following surgical biopsy. RESULTS: All three patients obtained rapid complete remission during their scheduled chemotherapy. One patient is alive without evidence of disease 12 months from the end of treatment. One patient, a frail, elderly gentleman, died due to massive pneumonia while in complete remission for two months. The third patient, who developed local recurrences in both parotid glands without transformation of his low-grade histology, achieved a second complete remission following chemo- and radiotherapy. All side effects were of a mild nature. CONCLUSION: Malignant lymphoma of the parotid gland is a chemo- and radiosensitive disease.

Pediatric thyroid carcinoma: 22 years of experience at the Northern Israel Oncology Center (1973-1995).

Over the past 22 years, 16 children with thyroid carcinoma were referred to the Northern Israel Oncology Center. All patients had undergone surgical procedures, either total or subtotal thyroidectomy, and 7 patients had undergone cervical lymph node dissections. Postoperatively, 5 patients underwent thyroid ablation with radioactive 131I as first treatment. Two patients received postoperative external radiation therapy to a field encompassing the cervical region, superior mediastinum, and both supraclavicular grooves. After a median follow-up of 60 months (range, 5-169 months), all patients are alive with no evidence of recurrent disease. Two patients who had recurrences, one in the submaxillary lymph nodes and one in the lungs, were salvaged successfully with retreatment with 131I therapy. No severe acute or long-term side effects were exhibited. The long-term results of treatment of pediatric thyroid carcinoma are excellent, but there remains disagreement over the extent of surgical and postsurgical treatment required.

Clinical activity of cisplatin and prolonged oral administration of etoposide in previously treated, anthracycline-resistant, metastatic breast cancer patients: a phase II study.

BACKGROUND: This phase II study evaluates the antitumor activity and tolerance of cisplatin and prolonged oral administration of etoposide in metastatic breast cancer previously exposed to anthracyclines. PROCEDURE: Twenty-seven patients with metastatic breast cancer who developed tumor progression following anthracyclines wer e entered in the study. The patients were treated with combination chemotherapy of cisplatin 50 mg/m(2) IV day 1 and oral etoposide 50 mg/m(2) days 1-17. Cycles were repeated every 29 days. RESULTS: Twenty-six patients were evaluated for toxicity and response. Complete remission was observed in 1 of 26 (4%) patients and partial remission in 12 of 26 (46%). Median duration of response was seven months. Pain relief was noted in 9 of 15 (60%) of the symptomatic patients. Myelosuppression was the major toxicity encountered and four (15%) patients required hospitalization for granulocytopenic fever. Nonhematologic toxicity was mild. CONCLUSIONS: The combination of cisplatin with prolonged oral etoposide is active and tolerable in the management of patients with relapsed metastatic breast cancer previously treated with an anthracycline-based regimen.

Carboplatin and etoposide for recurrent malignant glioma following surgical and radiotherapy failure: A clinical study conducted at the Northern Israel Oncology Center.

BACKGROUND AND OBJECTIVES: We conducted a phase II study using carboplatin and etoposide on patients with recurrent malignant glioma to investigate tumor response. METHODS: From January 1995 to March 1997, 21 patients with recurrent malignant glioma were treated with a carboplatin (300 mg/m(2), day 1)/etoposide (100 mg/m(2), days 1-3) regimen every 3-4 weeks. The following radiologic parameters were evaluated: tumor size, central lucency, degree of contrast enhancement, and mass effect. No patient had received chemotherapy previously. Dose escalation corresponded to hematologic tolerance and to general and neurologic performance status. Most patients were treated postoperatively with involved field radiotherapy followed by a boost to the tumor area, as defined on the presurgery computed tomography scan or on magnetic resonance imaging. Mean interval to introduction of chemotherapy was 8.8 months (range, 7-36 months). Patients received a mean of four cycles [range, 2-8 cycles]. RESULTS: Only 2 patients showed moderate radiological response, while 12 patients died of progressive disease. Mean time to progression following discontinuation of chemotherapy was 5.8 months (range, 1-11 months). The other patients survived with persistent disease and are being treated palliatively. Toxicity was manageable (1, neutropenic sepsis; 1, thrombocytopenia (45,000/mm(3)); 2, temporarily elevated transaminase level; 2, steroid-induced erosive gastritis). CONCLUSIONS: This phase II regimen proved to be ineffective in recurrent malignant glioma. Further studies incorporating innovative drug regimens and schedules are warranted. J. Surg. Oncol., 1999;71:167-170.

Sustained complete remission after chemobiohormonal therapy for metastatic melanoma.

The combination of carmustine, cisplatin, dacarbazine, interferon, and low-dose tamoxifen is widely used in treating metastatic melanoma and was originally reported to achieve a 20% complete response rate. Among 29 patients who completed the authors' phase II study with the regimen, five (17%) achieved complete remission, and the median duration of response was 8 months (range, 2-14 months). The aim of the study was to evaluate briefly the value and toxicity of this regimen in treating metastatic malignant melanoma.

A rare event of 5-fluorouracil-associated peripheral neuropathy: a report of two patients.

5-Fluorouracil (5-FU) is known to cause multifocal cerebral demyelination, which is pathologically related to a central inflammatory demyelinating process. To date, no case of peripheral neuropathy has been described after the administration of 5-FU alone. The authors describe two patients who had peripheral neuropathy that developed while they were receiving 5-FU-based chemotherapy.

Metastatic spinal cord compression as initial presentation of follicular thyroid carcinoma.

Follicular thyroid carcinoma, initially presenting as spinal cord compression due to metastatic lesions, is a less reported event. We present two cases of well-differentiated thyroid carcinoma that led to spinal cord compression. A thorough search of the literature revealed only five similar cases. We summarize the clinical characteristics of these cases, the therapeutic measures used, their outcome, and the prognosis.

Postsurgical etoposide-ifosfamide regimen in poor-risk nonmetastatic osteogenic sarcoma.

This prospective study was designed to test the activity of an ifosfamide-etoposide (VP-16) regimen on poor-risk, nonmetastatic, osteogenic sarcoma. A total of 13 patients with nonmetastatic osteogenic sarcoma with a poor histologic response to primary high-dose methotrexate-doxorubicin (Adriamycin)-cisplatinum chemotherapy received a total of six 5-day courses of ifosfamide (1,800 mg/m2) and etoposide (100 mg/m2) at three weekly intervals. The protocol was well tolerated, with only one case of transient renal failure. At present, eight patients (62%) have been in sustained complete remission with no evidence of recurrent disease for a mean follow-up of 3.4 years (range, 1.5-7.0 years). One patient is alive with lung metastases, and four have died of progressive disease. This prospective, albeit small, study confirms the efficacy of an ifosfamide-VP-16-based regimen in poor-risk, extremity, nonmetastatic osteogenic sarcoma. The demonstrated activity should spark large trials of ifosfamide-containing regimens in osteogenic sarcoma.

Radiation-induced tumors in irradiated stage I testicular seminoma: results of a 25-year follow-up (1968-1993).

BACKGROUND AND OBJECTIVES: Testicular seminoma is a very radiosensitive and curable cancer, with survival rates following radiation therapy within the range of 90-98% without apparent severe side effects. However, long-term survival following exposure to moderate-dose radiation therapy can result in radiation-induced tumors. METHODS: The incidence of radiation-induced tumors was determined in 81 irradiated stage I testicular seminoma patients treated at the Northern Israel Oncology Center (NIOC) from 1968 through 1993. RESULTS: Three (4%) patients developed second cancers within the high-dose volume. Indeed, those patients received a higher than usual dose to the para-aortic and pelvic regions. One patient, who developed inoperable pancreatic carcinoma, was treated with "hockey stick" field and mediastinal irradiation, plus, as a result of relapses, multiple cisplatin and VP-16 based regimens. CONCLUSIONS: The elimination of causative factors through lower total doses and field size reduction may reduce the, albeit very low, incidence of radiation-induced cancer in cured testicular seminoma.