Bleomycin-induced pneumonitis in three patients treated with chemotherapy for primary advanced seminoma.

PURPOSE: Bleomycin, etoposide and cisplatinum (BEP) comprise the most common regimen in the treatment of advanced testicular tumors, including seminoma. Common side effects are of hematologic, renal, and cardiovascular origin. One of the most prominent side effects is pulmonary toxicity attributed to bleomycin. We describe three patients who developed bleomycin-induced pneumonitis (BIP) with full recovery. METHODS: Pre-and post-treatment clinical, biochemical (including specific tumor markers) and radiological response assessment of 26 patients with primary advanced seminoma (AS) who were referred to our hospital for platinum-based chemotherapy between 1989-2010 are described. RESULTS: All patients were assessable for evaluation and all achieved long-term complete remission. Side effects were mild and manageable. Three patients developed bleomycin pulmonary toxicity after reaching cumulative doses of 180-240 units. All three patients presented with classical symptoms of non-productive cough, exertional dyspnea, and low-grade fever. Radiologically, the patients presented in the first months following completion of chemotherapy with initial bilateral interstitial and alveolar infiltrates, which worsened and progressed into consolidation and then regressed until total disappearance. All patients were treated with high-dose steroids and broad-spectrum antibiotics. CONCLUSION: AS is a very chemotherapy-responsive and sensitive disease, and approximately 90% of the patients enjoy complete regression of tumor masses and durable and sustained long-term survival with no evidence of disease. BIP may be a dangerous acute and chronic side effect, even in doses lower than 360 units. Considering the favorable clinical outcome of our patients, prompt diagnosis should be made and rapid medical intervention should be implemented.

Lack of HER-2 gene amplification and association with pathological and clinical characteristics of differentiated thyroid cancer.

Human epidermal growth factor receptor 2 (HER-2) is a well recognized prognostic and predictive factor in breast cancer. However, the role of HER-2 in thyroid cancer remains controversial. The aim of this study was to evaluate HER-2 expression in differentiated thyroid cancer (DTC) and determine whether there is an association with other clinical and pathological characteristics. A total of 69 patients with DTC were investigated, 58 of whom had papillary and 11 follicular carcinomas. HER-2 was detected by immunohistochemical examination on sections from formalin-fixed, paraffin-embedded tumor tissues. Tumors with HER-2 expression classed as +1 and +2 were retested with chromogenic in situ hybridization. Clinicopathological data were retrieved from the hospital records of the patients. HER-2 overexpression was found in 4 (6.9%) of the 58 patients with papillary carcinoma, whereas there was no HER-2 overexpression in any of the 11 cases of follicular carcinoma. There was no association of HER-2 expression with tumor size, pathological grade and cervical lymph node metastasis. In conclusion, there were no HER-2 positive cases of follicular carcinoma and the incidence of HER-2 overexpression in papillary carcinoma was very low. Thus, HER-2 cannot be used routinely as a prognostic or predictive factor in DTC. The expression of other epidermal growth factor receptors in DTC merits further investigation.

Radiotherapy for Stage IIA seminoma: The Northern Israel Oncology Center Experience, 1971-2010.

AIM: To evaluate treatment details, outcome, relapse rate and side-effects in Stage IIA seminoma irradiated and followed for a period of 39 years. BACKGROUND: Seminoma is a very radiosensitive disease and radiation therapy alone is able to achieve long-term disease-free survival, even in advanced Stage disease. Due to the lack of long-term prospective studies, it is of value to follow patients and try to determine the appropriate volume to be irradiated and the dose which can achieve total cure with minimal acute and chronic side-effects. PATIENTS AND METHODS: A retrospective review of 24 Stage IIA seminoma patients irradiated between 1971 and 2010 was performed. All patients underwent orchiectomy and meticulous clinical, biochemical and radiological staging. RESULTS: Median age at diagnosis was 36 years and median follow-up was 84 months. A majority of patients received the "hockey-stick" irradiation schedule (para-aortic lymph nodes and hemi-pelvis) to a total dose of 2250-2500 cGy and a boost to radiologically involved nodes of 500-1000 cGy. Treatment was well-tolerated. Twenty-one (88%) patients are alive with no evidence of disease. Two patients died due to unknown causes, while one patient died due to head of the pancreas carcinoma, most probably radiation-induced. CONCLUSIONS: In Stage II seminoma, radiotherapy can provide excellent results with low rates of toxicity. Reduction of total dose and size of fields without affecting the good results should be considered. Due to prolonged survival, awareness of second primary tumor is indicated.

Spermatocytic variant of classic seminoma: a report of five cases and a brief review of the literature.

BACKGROUND: Spermatocytic seminoma is a rare testicular malignancy, appearing in the adult population. It has a good prognosis and a low rate of metastatic potential. OBJECTIVES: We present five cases diagnosed and treated with radiotherapy at Rambam Health Care Campus in Haifa, Israel. METHODS: Between 1974 and 1996, five patients with stage I spermatocytic seminoma were referred post-orchiectomy to the Northern Israel Oncology Center. All five patients presented with the typical pathological features of the spermatocytic variant of classic seminoma, and all were staged clinically and radiologically. RESULTS: Mean age at diagnosis was 44 years (range 30-58 years). Main symptoms included a palpable testicular mass and/or testicular enlargement. Mean duration of symptoms was 9 months (range 0.5-24 months). Three patients were irradiated to the para-aortic/ipsilateral iliacal lymph nodes (mean total dose 2,500 cGy), one patient with 4,000 cGy. One patient was irradiated to the bilateral iliacal lymph nodes (2,600 cGy). With a median follow-up of 15 years, four patients are alive with no evidence of disease or severe late side effects. One patient developed severe lymphedema and symptomatic peripheral vascular disease, stage IIA prostate carcinoma (hormonal and brachytherapy treatment) and a non-secretory hypophyseal adenoma (surgically removed); he died at the age of 75 due to severe peripheral vascular and coronary heart disease with no evidence of his first or second primaries. CONCLUSIONS: Prognosis is excellent and does not differ from classic seminoma. As in the accumulated experience in early-stage, low-risk classic seminoma, we suggest surveillance as the preferred policy.

Anaplastic variant of classical seminoma of the testis: northern Israel oncology center experience and brief review of literature.

OBJECTIVES: There are only sporadic reports on the clinical behavior and appropriate treatment of anaplastic seminoma. This retrospective study summarizes our experience with the anaplastic variant of classical (typical) seminoma. METHODS: Between 1986 and 2006, seven anaplastic seminoma patients were staged and treated at the Northern Israel Oncology Center. Staging procedures included meticulous physical and neurological examinations, complete blood count, full biochemistry profile, specific tumor markers, testicular ultrasound, and other radiological measures. All patients underwent inguinal orchiectomy and were staged properly. Six patients had stage I disease, and one patient had stage IIA disease. Patients were irradiated with doses ranging from 2,500 to 3,000 cGy, and the stage IIA patient received an additional 1,000 cGy boost to radiographically involved lymph nodes. RESULTS: After a mean follow-up of 11 years, six patients are alive with no evidence of disease. One patient died due to an unknown, non-oncological, cause, unrelated to his previous testicular tumor, while in complete remission. CONCLUSIONS: Despite the low patient numbers and the retrospective nature of our study, it can be concluded that radiotherapy treatment for early-stage anaplastic seminoma patients might achieve the same excellent survival as for classical seminoma. However, the general consensus achieved through large-scale studies suggests that active surveillance should be offered to all stage I seminoma patients, regardless of the pathologic variant.

Platinum-based Chemotherapy in Primary Advanced Seminoma-a Retrospective Analysis: Treatment Results at the Northern Israel Oncology Center (1989-2010).

OBJECTIVE: Over the past 30 years, great strides have been made in the treatment of disseminated testicular tumors. Despite the low number of patients and the rarity of studies concerning primary advanced seminoma, the efficacy of chemotherapy is clear, mainly 3-4-cisplatin-based chemotherapy. Aiming to contribute to the understanding and implementation of proper chemotherapeutic management in advanced seminoma patients, we retrospectively summarized our experience with 26 patients who were referred for platinum-based chemotherapy, post-orchiectomy to the Northern Israel Oncology Center between 1989 and 2010. Response rate, side effects, and long-term outcome were investigated. METHODS: Before chemotherapy, meticulous staging was done, including tumor markers (B-human chorionic gonadotropin (B-HCG), alpha-fetoprotein (AFP), and lactic dehydrogenase (LDH)), and abdominal and pelvic computerized tomography (CT) scans were carried out. RESULTS: All 26 treated patients achieved complete remission, clinically and symptomatically, with normalization of their CT scans. At a median follow-up of 120 months (range, 24-268 months) all patients are alive, without evidence of recurrent disease. One patient whose disease recurred twice achieved a third complete remission following salvage treatment with high-dose chemotherapy and autologous peripheral stem cell transplantation. Another patient, who preferred surveillance, relapsed abdominally after 9 months but achieved long-standing complete remission with cisplatin-based chemotherapy. Both these patients are alive with no evidence of disease. Three patients recovered uneventfully from bleomycin-induced pneumonitis. CONCLUSIONS: Advanced seminoma is a highly curable disease using platinum-based chemotherapy. Our study confirms the efficacy and safety of cisplatin-based chemotherapy in the treatment of advanced seminoma.

Lack of HER-2 gene amplification in non-Hodgkin lymphoma using chromogenic in situ hybridisation test.

HER-2 is overexpressed in 25% of breast cancers and provides a poor prognostic factor, affecting treatment decisions including administration of trastuzumab. Single reports show a lack of HER-2 in non-Hodgkin lymphomas (NHLs) using immunohistochemical (IHC) test. The present study evaluates HER-2 in NHLs using the chromogenic in situ hybridisation (CISH) test, which is more accurate than IHC, to seek new prognostic factors. The secondary aim of the study is to investigate efficacy of using trastuzumab in the treatment of NHLs in future studies. Fifty eight formalin-fixed, paraffin-embedded tissue specimens presenting various NHLs were examined using CISH test. Sixty six percent of all patients were diagnosed at stages III and IV. Histologically, 30 (52%) were low grade and 28 (48%) were intermediate and high grade. HER-2 was negative in all NHLs. Because there is no HER-2 gene amplification in NHL, HER-2 cannot be used as a prognostic factor and should not play a role in biological targeting therapy in non-Hodgkin lymphoma.

Small cell (neuroendocrine) carcinoma of the prostate: etiology, diagnosis, prognosis, and therapeutic implications--a retrospective study of 30 patients from the rare cancer network.

Within the framework of the Rare Cancer Network Study, we examined 30 patients suffering from small cell neuroendocrine prostate cancer, either in an early/localized or an advanced/metastatic stage. Patients were treated with cisplatin-based chemotherapy, with or without pelvic radiotherapy. Two patients with early disease achieved complete remission for a duration of 19 and 22 months. Three patients with advanced disease achieved complete remission for 6, 7, and 54 months, respectively. Twenty-five patients succumbed to massive local and/or distant failure. No patient presented with brain metastases as the initial site of relapse. Small cell neuroendocrine prostate carcinoma is a very aggressive disease with a poor prognosis, even in its localized form. Despite initial response, the common cisplatin-based chemotherapy plus radiotherapy failed to improve outcome markedly. Improvement will come from understanding the biology of the disease and integrating new targeted therapies into the treatment of this rare and aggressive tumor.

Radiation therapy in prostate cancer.

Adenocarcinoma of the prostate is one of the most frequently diagnosed cancers of men in the Western hemisphere and is second only to lung cancer for male cancer mortality. Most patients are diagnosed in the early/clinically localized stage, which can be treated curatively with radiation therapy alone. Innovative methods such as brachytherapy, three-dimensional conformal radiotherapy (3D-CRT), and IMRT (intensity modulated radiotherapy) are able to deliver very high tumoricidal doses to the diseased prostate, with minimal side effects to the surrounding tissue. Radiation therapy combined with hormonal treatment can be curative in locally advanced disease. Radiation therapy is also very effective in alleviating symptoms of metastatic prostate cancer (bone metastases, spinal cord compression, and bladder outlet obstruction).

[Molecular portrait of breast cancer with sub-classification of breast tumor].

Malignant breast tumors display a wide variety of clinical and pathological features. The rapid development of molecular technologies over the last decade, using micro-array and expression studies to assess human diseases, has revolutionized the field of breast cancer characterization. The technique is based on simultaneous assessment of thousands of genes used to define the metabolic status of tumor cells and their active interaction with the microenvironment. Using hierarchal clustering to profile tumors according to expression of intrinsic genes, locally advanced breast cancers were classified into several major sub-groups, including: 1. Luminal-epithelial group (with sub-classification into types A and B), characterized by expression of the estrogen receptor and genes associated with the estrogenic function; 2. Basal-epithelial group, typically negative for the estrogen and progesterone receptors and the Her2/neu oncogene; 3. ERBB2+ group associated with over expression of the Her2 amplicone; 4. Normal breast-like group. Those sub-groups are the results of different pathophysiological processes, and their clinical outcomes are unique and predictable. Using supervised analysis, in which clinical outcome is pre-defined, several "poor prognostic expression signatures" were found to be associated with an increased risk of relapse, including: a 70-gene cluster in young patients with node-negative tumors, expression signature characteristic of the wound-response activity in node-positive and/or negative tumors, and the Oncotype DX system relevant for risk stratification and systemic treatment recommendations in node-negative receptor-positive tumors. Benefits and limitations of those methods and future directions are discussed.

Central neurologic involvement in mycosis fungoides: ten cases, actuarial risk assessment, and predictive factors.

BACKGROUND: Neurologic involvement in mycosis fungoides is rare. Isolated case reports in the literature suggest the pattern and the natural history for such occurrences, while a literature summary can provide direction on diagnosis and management. Although case series may confirm such information, cohort data are required to establish an overall risk of occurrence and to evaluate possible predictive factors. METHODS: We presented a case of central nervous system involvement in mycosis fungoides from Haifa, Israel and tabulated a series of nine cases from Canada. To estimate the risk of neurologic involvement, a cohort of 680 consecutive patients with newly diagnosed mycosis fungoides, of which the nine cases of neurologic involvement emerged during follow up, was analyzed using the Kaplan-Meier method. The actuarial risk of developing neurologic involvement was related to the baseline tumor-node-metastasis-blood classification factors. RESULTS: The pattern of disease in these 10 additional cases confirms the overall pattern in the approximately 40 patients described in the literature. The main symptoms are fluctuating higher cognitive functions and cranial nerve dysfunction, with fairly rapid clinical onset of symptoms. Most cases of central neurologic involvement with mycosis fungoides emerge within a setting of advanced disease. In patients with newly diagnosed mycosis fungoides, the greatest risk of developing neurologic involvement is within the first several years after diagnosis and is associated with the initial stage of disease. Patients with two or more of the T3-4, N3, M1, and B1 classification factors have a one in six chance of developing central neurologic involvement, while there is about a one in a hundred chance for the corresponding control group. CONCLUSIONS: Neurologic involvement with mycosis fungoides is indeed rare, but it is associated with a more advanced stage at diagnosis and with other visceral disease that can precede it. Although the role of low-dose prophylactic cranial radiation is uncertain, overt neurologic involvement requires urgent palliative treatment.

Prevention of chemotherapy-induced neutropenia by special honey intake.

Febrile neutropenia is a serious side effect of chemotherapy. Colony-stimulating factors (CSFs) are used for primary and secondary treatment in patients with grade 4 neutropenia. The use of CSFs is expensive and accompanied by side effects. In the current study, Life-Mel Honey (LMH) was administered to prevent neutropenia and to reduce the need for CSFs in patients treated with chemotherapy. Thirty cancer patients receiving chemotherapy for primary or metastatic disease were included. All patients had grade 4 neutropenia and were treated with CSFs. The patients repeated the same chemotherapy schedule, with the addition of LMH for 5 d. Blood count was performed weekly. There was no recurrence of neutropenia after LMH intake and no need for treatment with CSFs in 12 (40%) of patients. Eighteen (60%) patients with LMH developed neutropenia grade 4 and were treated with CSFs (p=0.007). Hemoglobin levels remained >11 g/dL during LMH intake in 19 (64%) patients. Only three (10%) patients had thrombocytopenia. Eight (32%) patients reported improvement in quality of life. The use of LMH in patients who are at high risk of developing neutropenia as a result of chemotherapy decreases the risk of pancytopenia and the need for CSFs. LMH is inexpensive, has no side effects, and is easy to administer.

P53 alteration in oral tongue cancer is not significantly associated with age at diagnosis or tobacco exposure.

AIMS AND BACKGROUND: The tumor suppressor gene P53 is mutated in almost half of head and neck cancers. The current work assessed the prognostic significance of P53 alteration in patients with squamous cell carcinoma of the oral tongue treated with a curative intent, its association with age at diagnosis (using 45 years as a cut point), and risk exposure as defined by tobacco and/or alcohol consumption. METHODS: P53 alteration was determined immunohistochemically in 45 patients with tongue cancer treated with a curative intent. RESULTS: P53 alteration occurred in 20 of 45 tumors (44%) and was more common among younger patients (58% versus 36% for younger versus older patients, respectively) and those lacking tobacco/alcohol exposure (53% versus 40% for "no-risk" and "risk" groups, respectively), but the differences were not statistically significant. With a median follow-up of 56 months, 5-year progression-free survival rates were 48% and 66% in patients with and without P53 detection, respectively (P = 0.22). CONCLUSIONS: Despite a trend of a younger age at diagnosis in P53-altered tumors, results did not reach statistically significant differences. A trend of a worse clinical outcome with P53 alteration was noted.

Primary pure squamous cell carcinoma of the breast.

Primary squamous cell carcinoma (SCC) of the breast is an extremely rare tumor. It is diagnosed when the malignant cells are entirely of squamous type, the tumor is independent from overlying skin, and other primary SCC sites are excluded. This report presents clinical, radiologic, and histologic correlative findings of a patient diagnosed with pure SCC of the breast. Literature review suggests that primary SCC tumors of the breast are large, often cystic lesions, with a low rate of nodal involvement, no expression of estrogen and progesterone receptors, and resistance to the chemotherapy regimens commonly used in breast cancer.

Efficacy of I131 ablation therapy using different doses as determined by postoperative thyroid scan uptake in patients with differentiated thyroid cancer.

PURPOSE: The optimal dose of I(131) for ablation of functioning residual thyroid tissue after surgery is controversial. The current study was conducted to determine the optimal dose of I(131) for remnant postoperative ablation. A review of the literature is included. METHODS AND MATERIALS: A total of 238 patients with papillary and follicular carcinoma were treated with I(131) for ablation of a postoperative thyroid remnant. The I(131) dose was based on the 24-h percentage of neck uptake in the postoperative thyroid scans. Patients with < 5% uptake received a median of 85 mCi; 6-10% uptake, a median of 80 mCi; 11-15% uptake, a median of 60 mCi; 16-20% uptake, a median of 50 mCi; and > or =21% uptake, a median of 30 mCi. The ablation results were compared with the prognostic factors. RESULTS: Complete ablation was observed in 40 (92%) of 43 patients receiving 85 mCi, in 31 (94%) of 33 who received 80 mCi, in 39 (95%) of 41 who received 60 mCi, in 51 (93%) of 55 who received 50 mCi, in 37 (94%) of 39 who received 30 mCi, and in 18 (96%) of 19 who received 30 mCi. The overall successful ablation rate was 94% (95% confidence interval, 89-100%). CONCLUSION: Our findings suggest that patients with differentiated thyroid cancer can be treated with doses of I(131) according to the percentage of neck uptake of postoperative total body scan, with high complete ablation rates, without exposing patients to higher dose levels of I(131).

Breast cancer in women with recent exposure to fertility medications is associated with poor prognostic features.

BACKGROUND: Fertility drug therapy (FDT) induces supraphysiologic endogenous estrogen production and might transiently increase breast cancer risk. Tumors developing following FDT exposure have not been extensively studied. METHODS: Thirty-eight breast cancer patients with 40 primary tumors and with history of FDT exposure were identified and compared with two other breast cancer groups: women with pregnancy-associated breast cancer (PABC, 22 patients with 23 tumors) and premenopausal women born during same calendar years and not exposed to hormonal manipulations or recent pregnancy (controls, 192 patients with 201 tumors). Patients were diagnosed and treated mostly during the last decade. RESULTS: Compared with controls, tumors of patients with FDT exposure presented at advanced stages (P <.005), were more likely to be estrogen or progesterone receptor negative (P <.03) and of poor histology grade (P <.0002). Aggressive features predominated among women diagnosed within 2 years of an FDT cycle (P <.05). FDT and PABC groups shared similarities. With a median follow-up of 43 months, relapse-free and cancer-free survival rates were significantly reduced in the FDT and PABC groups (P <.01 and P <.01, respectively). Multivariate analysis revealed only treatment-defined tumor stage (operable, locally advanced, or metastatic) as predictive of survival (P <.0001). CONCLUSION: Breast tumors in women with recent FDT exposure present with poor prognostic features and share similarities with PABC. Survival is stage dependent.

Interstitial brachytherapy in soft tissue sarcomas: the Rambam experience.

BACKGROUND: There are radiobiologic and technical advantages to the use of interstitial brachytherapy alone or as an adjunct to external beam radiotherapy in the postoperative treatment of soft tissue sarcomas. OBJECTIVES: To review the experience of the Rambam Medical Center in implementing interstitial brachytherapy in the treatment of 32 patients with soft tissue sarcomas. METHODS: Thirty-two patients with variously located soft tissue sarcomas were managed with a combination of surgery and brachytherapy of the tumor bed, with or without EBRT. In 27 of 32 patients, brachytherapy catheters were placed intraoperatively, while in 5 patients the implant was performed as a separate postoperative procedure. Twenty-seven patients received low dose-rate brachytherapy with Iridium-192 seeds. Five patients received fractionated high dose-rate brachytherapy using the microSelectron machine. RESULTS: With a median follow-up of 36 months, the overall local control rate was 87.5%. Four of 32 patients (13%) failed locally at the implant site, and 6 (19%) developed lung metastasis. Two of the five patients with lung metastasis had a local recurrence as well. At the time of analysis, eight patients had died of sarcoma (disease-specific mortality rate was 25%), while three had died of intercurrent causes. The 5 year actuarial disease-free survival rate was 56%, and the 5 year actuarial overall survival 70%. Five patients (16%) developed severe wound complications following surgery/brachytherapy, and six patients (19%) developed late local toxicity (fibrosis and telangiectasia). CONCLUSIONS: Wide local excision followed by interstitial brachytherapy has resulted in an 87.5% local control rate with a 16% local complication rate.

Pure versus follicular variant of papillary thyroid carcinoma: clinical features, prognostic factors, treatment, and survival.

BACKGROUND: The follicular variant of papillary thyroid carcinoma (FVPTC) is a common subtype of papillary thyroid carcinoma. Few studies have compared the clinical behavior and treatment outcome of patients with FVPTC with the outcome of patients with pure papillary carcinoma (PTC). A retrospective study was performed to identify the influence of FVPTC compared with PTC on therapeutic variables, prognostic variables, and survival. METHODS: A clinicopathologic analysis of 243 patients with papillary carcinoma was performed. One hundred forty-three tumors were PTC, and 100 tumors were FVPTC. The following variables were evaluated: age at diagnosis, tumor size, stage of tumor, treatment, capsular invasion, and survival. RESULTS: The median follow-up was 11.5 years. The median age was 43 years in the PTC group and 44 years in the FVPTC group. The median tumor size, disease stage, and type of initial surgery and iodine 131 ablation were similar. More patients had capsular invasion by the tumor and less metastases to cervical lymph nodes in the FVPTC group. The actuarial survival of patients age < 40 years was higher compared with the survival of patients age > 50 years in both groups. The 21-year overall actuarial survival was 82% in patients with PTC and 86% in patients with FVPTC (P value not significant). CONCLUSIONS: The pathologic and clinical behaviors of PTC and FVPTC were comparable. Prognostic factors, treatment, and survival also were similar. Patients in both groups must be treated identically.