Anti-androgen for myoepithelial tumor: a potent therapy yet a potential misleader.

Myoepithelial tumor is a rare form of cancer, mainly arising from the salivary glands and extremities. Due to its rarity, no formal treatment guidelines exist. Here we report a case of a male patient diagnosed with metastatic myoepithelial tumor which was successfully treated with an androgen-receptor (AR) antagonist (bicalutamide), based on the results of molecular testing. Six years after the initiation of bicalutamide, patient was diagnosed with metastatic prostate cancer. To our knowledge, this is the first case described in literature that demonstrate the effectiveness of anti-androgens in treating myoepithelial tumor. Vigilance should be maintained when screening these patients for prostate cancer as their 'true' prostate specific antigen levels might be masked by the ongoing endocrine therapy.

Acute and late side-effects after low dose-rate brachytherapy for prostate cancer; incidence, management and technical considerations.

PURPOSE: To review common reported side effects and complications after primary LDR-BT (monotherapy) and discuss some of the technical aspects that could impact the treatment outcomes. METHODS AND MATERIALS: A literature search was undertaken using medical subject headings (MeSH) complemented by the authors' personal and institutional expertise. RESULTS: The reported incidence of acute and late grade 2 or above urinary, bowel and sexual side effects is very variable across the literature. The learning curve and the implant quality have a clear impact on the toxicity outcomes. Being aware of some of the technical challenges encountered during the procedure and ways to mitigate them could decrease the incidence of side effects. Careful planning of seed placement and seed deposition allow sparing of the organs at risk and a lower incidence of urinary and gastro-intestinal toxicity. CONCLUSIONS: Low dose-rate brachytherapy remains a standard monotherapy treatment in the setting of favorable-risk prostate cancer. High disease control and low long-term toxicities are achievable in expert hands with a good technique.

Impact of daily soft-tissue image guidance to prostate on pelvic lymph node (PLN) irradiation for prostate patients receiving SBRT.

PURPOSE: To determine the impact of using fiducial match for daily image-guidance on pelvic lymph node (PLN) coverage for prostate cancer patients receiving stereotactic body radiation therapy (SBRT). METHODS: Thirty patients underwent SBRT treatment to the prostate and PLN from 2014 to 2016. Each patient received either 800cGy × 5 or 500cGy × 5 to the prostate and 500cGy × 5 to the PLN. A 5 mm clinical target volume (CTV)-to-planning target volume (PTV) margin around the PLN was used for planning. Two registrations with planning computed tomography (PCT) for each of the daily cone beam CTs (CBCTs) were performed: a rigid registration to fiducials and to the bony anatomy. The average translational difference between fiducial and bony match as well as percentage of fractions with differences > 5mm were calculated. Changes in bladder and rectal volume as well as center-of-mass (COM) position from simulation parameters, and their correlation with translational difference were also evaluated. The dosimetric impact of the translational differences was calculated by shifting the plan isocenter. RESULTS: The average translational difference between fiducial and bony match was 0.06 ± 0.82, 2.1 ± 4.1, -2.8 ± 4.3, and 5.5 ± 4.2 mm for lateral, vertical, longitudinal, and vector directions. The average change in bladder and rectal volume from simulation was -67.2 ± 163.04 cc (-12 ± 52%) and -1.6 ± 18.75 (-2 ± 30%) cc. The average change in COM of bladder from the simulation position was 0.34 ± 2.49, 4.4 ± 8.1, and -3.9 ± 7.5 mm along the LR, AP, and SI directions. The corresponding COM change for the rectum was 0.17 ± 1.9, 1.34 ± 3.5, and -0.6 ± 5.2 mm. CONCLUSIONS: The 5 mm margin covered ~75% of fractions receiving PLN irradiation with SBRT, daily CBCT and fiducial-guided setup. The dosimetric impact on PLN coverage was significant in 19% of fractions or 25% of patients. A larger translational shift was due to variation in rectal volume and changes in COM position of the bladder and rectum. A consistent bladder positioning and/or rectum filling compared with presimulation volume were essential for adequate coverage of PLN in a hypofractionated treatment regime.

Stereotactic prostate focal reirradiation therapy for local recurrence: preliminary results of Hartmann Oncology Radiotherapy Group.

OBJECTIVE: Our objective was to report our experience and to evaluate the feasibility and toxicity of focal salvage stereotactic body radiation therapy (SBRT) in patients with post-radiation local recurrence of prostate cancer. METHODS: We retrospectively reviewed medical records of patients treated with Cyberknife ® between October 2014 and April 2017 at our institution for a focal reirradiation delivered to the prostate/prostatic bed for local recurrence after radical or adjuvant radiotherapy. All patients underwent prostate biopsies at recurrence at the time of fiducial markers placement, had choline PET/CT and pelvic MRI. The treatment consisted in 36 Gy in six fractions delivered every other day. Post reirradiation toxicities were assessed according to the CTCAE v4 (Common Terminology Criteria for Adverse Events). RESULTS: 42 patients were treated with followed with a median follow-up of 21 months (range 3 - 31). 34 patients had biopsy proven recurrence. The initial treatment was radical prostatectomy and radiation therapy for 9 patients and radiation therapy alone for 33 patients. 23 patients from the group of prostate reirradiation had placement of rectal spacers. No Grade 4 or 5 toxicity were observed. 27 acute urinary events were recorded: 18 patients experienced Grade 1, 9 patients experienced Grade 2 toxicity and 1 patient experienced Grade 3 urinary toxicity, namely cystitis and/or dysuria. No Grade 2 or more digestive toxicity was observed. Rectal doses were significantly lower with rectal spacers. CONCLUSION: Salvage focal Cyberknife ® seems feasible and show promising results. ADVANCES IN KNOWLEDGE: SBRT for local prostate cancer recurrence after initial radiotherapy is well tolerated with short follow-up.

Placement of an absorbable rectal hydrogel spacer in patients undergoing low-dose-rate brachytherapy with palladium-103.

PURPOSE: Rates of rectal toxicity after low-dose-rate (LDR) brachytherapy for prostate cancer are dependent on rectal dose, which is associated with rectal distance from prostate and implanted seeds. Placement of a hydrogel spacer between the prostate and rectum has proven to reduce the volume of the rectum exposed to higher radiation dose levels in the setting of external beam radiotherapy. We present our findings with placing a rectal hydrogel spacer in patients following LDR brachytherapy, and we further assess the impact of this placement on dosimetry and acute rectal toxicity. METHODS AND MATERIALS: Between January 2016 and April 2017, 74 patients had placement of a hydrogel spacer, immediately following a Pd-103 seed-implant procedure. Brachytherapy was delivered as follows: as a monotherapy to 26 (35%) patients; as part of planned combination therapy with external beam radiotherapy to 40 (54%) patients; or as a salvage monotherapy to eight (11%) patients. Postoperative MRI was used to assess separation achieved with rectal spacer. Acute toxicity was assessed retrospectively using Radiation Oncology Therapy Group radiation toxicity grading system. Rectal dosimetry was compared with a consecutive cohort of 136 patients treated with seed implantation at our institution without a spacer, using a 2-tailed paired Student's t test (p < 0.05 for statistical significance). RESULTS: On average, 11.2-mm (SD 3.3) separation was achieved between the prostate and the rectum. The resultant mean rectal volume receiving 100% of prescribed dose (V100%), dose to 1 cc of rectum (D1cc), and dose to 2 cc of rectum (D2cc) were 0 (SD 0.05 cc), 25.3% (SD 12.7), and 20.5% (SD 9.9), respectively. All rectal dosimetric parameters improved significantly for the cohort with spacer placement as compared with the nonspacer cohort. Mean prostate volume, prostate V100 and dose to 90% of gland (D90) were 29.3 cc (SD 12.4), 94.0% (SD 3.81), and 112.4% (SD 12.0), respectively. Urethral D20, D5cc, and D1cc were 122.0% (SD 17.27), 133.8% (SD 22.8), and 144.0% (SD 25.4), respectively. After completing all treatments, at the time of first the followup, 7 patients reported acute rectal toxicity-6 experiencing Grade 1 rectal discomfort and 1 (with preexisting hemorrhoids) experiencing Grade 1 bleeding. CONCLUSIONS: Injection of rectal spacer is feasible in the post-LDR brachytherapy setting and reduces dose to the rectum with minimal toxicity. Prostate and urethral dosimetries do not appear to be affected by the placement of a spacer. Further studies with long-term followup are warranted to assess the impact on reduction of late rectal toxicity.

Post-translational Regulation of Radioactive Iodine Therapy Response in Papillary Thyroid Carcinoma.

Background: Radioactive iodine (RAI) is the mainstay of treatment for differentiated thyroid carcinoma (DTC). Nevertheless, the mechanism of RAI resistance that occurs in many patients with DTC remains unknown. We aimed to elucidate the role of post-translational regulation of radioiodine uptake. Methods: We analyzed the expression pattern of the ribosomal glycosylphosphatidylinositol transamidase (GPIT) complex in freshly excised tumors from 10 patients with DTC. We used functional RAI uptake assays to assess the role of GPIT in iodine uptake both in vivo and in vitro. The effects of MEK inhibition on the GPIT subunit PIGU and the sodium iodide symporter (NIS) were assessed in three DTC cell lines and in four human DTC biopsies. We used a multivariable logistic regression model to study the role of PIGU in the response to RAI treatment in advanced DTC. All statistical tests were two-sided. Results: Expression profiling of different GPIT complex subunits revealed statistically significantly lower expression of PIGU in papillary carcinomas than in matched normal thyroid tissue (P < .001). Expression of PIGU in the K1 human papillary carcinoma cell line resulted in a robust increase in NIS glycosylation and trafficking to the cell membrane, accompanied by a robust increase in I125 uptake both in vitro (465 200 ± 56 343 vs 1236 ± 156 counts per million, P < .001) and in vivo (128 945 ± 28 556 vs 7963 ± 192 counts per million, P < .001, n = 5 mice per group). Treatment with the MEK inhibitors U0126 and PD302 rescued PIGU expression. Finally, the PIGU expression levels in tumors of 18 patients with recurrent DTC were associated with a biochemical response to RAI treatment (hazard ratio = 8.06, 95% confidence interval = 3.72 to 12.3, P = .001). Conclusions: We showed that downregulation of PIGU in DTC determines NIS function and RAI avidity. This represents a novel mechanism for RAI resistance.

Perineural Spread in Noncutaneous Head and Neck Cancer: New Insights into an Old Problem.

Head and neck malignancies have the propensity to invade nerves. Perineural tumor invasion is common, with some series reporting rates of 30 to 100%. Squamous cell carcinoma and adenoid cystic carcinoma are the most commonly involved tumors. The most commonly involved nerves are the trigeminal (cranial nerve [CN] V) and facial (CN VII) and their branches. Neural spread away from a tumor is encountered less often and usually causes specific symptoms such as pain, muscle weakness, and atrophy, depending on the involved nerves. While clinical symptoms and physical examination may suggest the presence of neural invasion, specific imaging modalities such as fat-suppressed T1-weighted magnetic resonance images, should be utilized to identify perineural tumor spread in its early phases. Perineural tumor spread should be considered and addressed in the treatment planning of patients with head and neck or skull base cancers as it can influence the extent of surgery, and the dosage and fields of radiation therapy. In the current review, we discuss the clinical course of perineural tumor spread and its therapeutic implications.

External Beam Radiation in Differentiated Thyroid Carcinoma.

The treatment of differentiated thyroid carcinoma (DTC) is surgery followed in some cases by adjuvant treatment, mostly with radioactive iodine (RAI). External beam radiotherapy (EBRT) is less common and not a well-established treatment modality in DTC. The risk of recurrence depends on three major prognostic factors: extra-thyroid extension, patient's age, and tumor with reduced iodine uptake. Increased risk for recurrence is a major factor in the decision whether to treat the patient with EBRT. Data about the use of EBRT in DTC are limited to small retrospective studies. Most series have demonstrated an increase in loco-regional control. The risk/benefit from giving EBRT requires careful patient selection. Different scoring systems have been proposed by different investigators and centers. The authors encourage clinicians treating DTC to become familiarized with those scoring systems and to use them in the management of different cases. The irradiated volume should include areas of risk for microscopic disease. Determining those areas in each case can be difficult and requires detailed knowledge of the surgery and pathological results, and also understanding of the disease-spreading pattern. Treatment with EBRT in DTC can be beneficial, and data support the use of EBRT in high-risk patients. Randomized controlled trials are needed for better confirmation of the role of EBRT.

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.

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.

Pegfilgrastim overdose: case report and review of the literature.

Single-dose pegfilgrastim is commonly used for the prophylaxis of neutropenia in patients receiving myelotoxic chemotherapy. We report a case of a 69-year-old man who was treated with chemotherapy for small-cell lung cancer and mistakenly self-administered a 36 mg overdose of pegfilgrastim, a sixfold increase over the scheduled dose.