Dose to the dominant intraprostatic lesion using HDR vs. LDR monotherapy: A Phase II randomized trial.

PURPOSE: To present the dosimetric results of a Phase II randomized trial comparing dose escalation to the MRI-defined dominant intraprostatic lesion (DIL) using either low-dose-rate (LDR) or high-dose-rate (HDR) prostate brachytherapy. MATERIAL AND METHODS: Patients receiving prostate brachytherapy as monotherapy were randomized to LDR or HDR brachytherapy. Prostate and DILs were contoured on preoperative multiparametric MRI. These images were registered with transrectal ultrasound for treatment planning. LDR brachytherapy was preplanned using I-125 seeds. HDR brachytherapy used intraoperative transrectal ultrasound-based planning to deliver 27 Gy/2 fractions in separate implants. DIL location was classified as peripheral, central, or anterior. A student t-test compared DIL D90 between modalities and DIL locations. RESULTS: Of 60 patients, 31 underwent LDR and 29 HDR brachytherapy. Up to three DILs were identified per patient (100 total) with 74 peripheral, six central, and 20 anterior DILs. Mean DIL volume was 1.9 cc (SD: 1.7 cc) for LDR and 1.6 cc (SD 1.3 cc) for HDR (p = 0.279). Mean DIL D90 was 151% (SD 30%) for LDR and 132% (SD 13%) for HDR. For LDR, mean peripheral DIL D90 was 159% (SD 27%) and central or anterior 127% (SD 13%). HDR peripheral DILs received 137% (SD 12%) and central or anterior 119% (SD 7%). DIL D90 for peripheral lesions was higher than anterior and central (p < 0.001). CONCLUSIONS: DIL location affects dose escalation, particularly because of urethral proximity, such as for anterior and central DILs. HDR brachytherapy may dose escalate better when target DIL is close to critical organs.

Papillary thyroid microcarcinoma: an over-treated malignancy?

BACKGROUND: The clinical importance of papillary thyroid microcarcinoma (PTMC) remains controversial, with current guidelines suggesting that thyroid lobectomy alone is sufficient. The purpose of this study was to identify population-level treatment patterns in the USA for PTMC. METHODS: Patients with PTMC in SEER (1998-2010) were included; demographic, clinical (extent of surgery, administration of post-operative radioactive iodine [RAI]), and pathologic characteristics were examined. Outcomes of interest were 5- and 10-year overall survival (OS) and disease-specific survival (DSS). RESULTS: The cohort consisted of 29,512 patients. Mean age at diagnosis was 48.5 years; mean tumor size was 0.53 cm. Overall, 73.4 % of patients underwent total thyroidectomy, and RAI was administered to 31.3 %. In multivariate analysis, total thyroidectomy was more frequently performed in patients with multifocal (odds ratio [OR] 2.55), 'regional', or 'distant' PTMC (OR 2.90 and 2.59). Non-operative management was associated with male patients (OR 4.24) and those aged ≥65 years (OR 6.31). Post-operative RAI was associated with multifocal PTMC (OR 2.57). Overall, 5- and 10-year DSS was 99.6 and 99.3 %, respectively, with no difference in DSS between patients who underwent partial versus total thyroidectomy. OS of patients with PTMC who underwent any thyroid operation was similar to that of the general population of the USA. CONCLUSIONS: An increasing number of patients are undergoing total thyroidectomy and RAI for PTMC. While there may be a subset of patients for whom more aggressive therapy is indicated, many patients with PTMC may be over-treated, with no demonstrable benefit to survival.

Parathyroid carcinoma and oxyphil parathyroid adenoma: an uncommon case of misinterpretation in clinical practice.

A 46 year-old male presented with persistently high level of serum parathyroid hormone (PTH), despite successful resection of an oxyphilic cell parathyroid adenoma of the left lower gland. Renal function and serum calcium were normal, leading to vitamin D deficiency being considered. Tc99m-sestamibi parathyroid scintigraphy showed no capitation, but a cervical ultrasound demonstrated an increase in the lower parathyroids. Surgery confirmed that the right gland was normal but the left corresponded to parathyroid carcinoma. The patient developed severe hypocalcemia, with PTH values being consistent with hypoparathyroidism for a few months. However, a progressive increase in calcium and PTH serum levels indicated recurrence of disease. Tc99m-sestamibi scintigraphy demonstrated hyperfixation in topography of the left inferior parathyroid and the patient was subjected to a third and more extensive surgery, with removal of lymph nodes and adjacent thyroid tissue. Serum calcium and PTH remained elevated, requiring loop diuretics and intravenous bisphosphonates to control hypercalcemia. Cervical radiotherapy was implemented as adjuvant therapy. After two months the patient complained of dyspnea, and a CT scan of the chest demonstrated areas of parenchymal condensation, suggestive of actinic pneumonitis. At the 2-year follow-up no major issues were evident.

Sentinel lymph node biopsy performed after neoadjuvant chemotherapy is accurate in patients with documented node-positive breast cancer at presentation.

BACKGROUND: The optimal strategy for incorporating lymphatic mapping and sentinel lymph node biopsy into the management of breast cancer patients receiving neoadjuvant chemotherapy remains controversial. Previous studies of sentinel node biopsy performed following neoadjuvant chemotherapy have largely reported on patients whose prechemotherapy, pathologic axillary nodal status was unknown. We report findings using a novel comprehensive approach to axillary management of node-positive-patients receiving neoadjuvant chemotherapy. METHODS: We evaluated 54 consecutive breast cancer patients with biopsy-proven axillary nodal metastases at the time of diagnosis that underwent lymphatic mapping with nodal biopsy as well as concomitant axillary lymph node dissection after receiving neoadjuvant chemotherapy. All cases were treated at a single comprehensive cancer center between 2001 and 2005. RESULTS: The sentinel node identification rate after delivery of neoadjuvant chemotherapy was 98%. Thirty-six patients (66%) had residual axillary metastases (including eight patients that had undergone resection of metastatic sentinel nodes at the time of diagnosis), and in 12 cases (31%) the residual metastatic disease was limited to the sentinel lymph node. The final, post-neoadjuvant chemotherapy sentinel node was falsely negative in three cases (8.6%). The negative final sentinel node accurately identified patients with no residual axillary disease in 17 cases (32%). CONCLUSIONS: Sentinel lymph node biopsy performed after the delivery of neoadjuvant chemotherapy in patients with documented nodal disease at presentation accurately identified cases that may have been downstaged to node-negative status and can spare this subset of patients (32%) from experiencing the morbidity of an axillary dissection.

t(8;16) AML developed subsequent to breast cancer therapy.

We report a breast cancer patient who developed acute myeloid leukemia (AML) one year following her adjuvant chemotherapy consisting of cyclophosphamide, adriamycin and 5-fluorouracil. Cytogenetic examination of bone marrow samples resulted in t(8;16)(p11.2;p13.3), which is a chromosome rearrangement observed in de novo and treatment related AML M4/M5 with a poor prognosis.

[Bilateral thalamic gliomas: report of a case with cognitive impairment]. / Glioma talámico bilateral: presentación de un caso con deterioro cognitivo.

INTRODUCTION: Bilateral thalamic tumours are very rare and have been recently identified as a subgroup of thalamic neoplasms due to their characteristic clinical presentation, with behavioural and memory disorders and without sensory or motor changes. We describe a patient who presented with mood and behaviour changes due to a bilateral thalamic glioma, discuss the literature related to these rare neoplasms and review the anatomical bases of their particular clinical presentation. CASE REPORT: A 67-year-old woman consulted because of behavioural changes and frequent forgetfulness. Neurological examination was normal except from a deficit in the retention of words and numbers. MR images revealed bilateral thalamic swelling by a isointense in T1, hyperintense in T2 and protonic density mass that did not enhance. The tumour was diagnosed as an astrocytoma by stereotactic biopsy. She continued to deteriorate and a year after diagnosis she was bedridden and with a severe dementia. CONCLUSION: Bithalamic tumors, as other lesions that affect the thalamus bilaterally, characteristically present with mood and behaviour changes and memory impairment.

Dosimetric study of boron neutron capture therapy with borocaptate sodium (BSH)/lipiodol emulsion (BSH/lipiodol-BNCT) for treatment of multiple liver tumors.

PURPOSE: We performed a computational study to investigate the feasibility of borocaptate sodium (BSH)/lipiodol-boron neutron capture therapy (BSH/lipiodol-BNCT) for multiple liver tumors using Simulation Environment for Radiotherapy Applications (SERA), a currently available BNCT treatment planning system. METHODS AND MATERIALS: Three treatment plans for BSH/lipiodol-BNCT using two or three epithermal neutron beams in one fraction were generated for 4 patients with multiple liver tumors using the SERA system. The (10)B concentrations in the tumor and the liver assumed in the study were 197.3 and 15.3 ppm, respectively; and were obtained from experimental studies in animals. The therapeutic gain factors for the liver tumors, defined as the minimum dose to the tumor/maximum dose to the liver, and the inhomogeneity index of the thermal neutron fluence for the whole of the liver, defined as the maximum neutron fluence - minimum neutron fluence/mean neutron fluence, were evaluated in each plan. RESULTS: Three epithermal neutron beams incident on the anterior, posterior, and right side of the patient can deliver the most homogeneous distribution of thermal neutron fluence to the whole of the liver and provide the greatest therapeutic gain factors for tumors in the right lobe and approximately equal therapeutic gain factors for tumors in the left lobe, compared with the two opposed (anterior-posterior) and two orthogonal (anterior-right) beams. CONCLUSIONS: From a dosimetric viewpoint, the BSH/lipiodol-BNCT treatment plan using three epithermal neutron beams is the most suitable for the treatment of multiple liver tumors.

Risk of lymphedema after regional nodal irradiation with breast conservation therapy.

PURPOSE: To evaluate the risk factors for lymphedema in patients receiving breast conservation therapy for early-stage breast cancer. METHODS AND MATERIALS: Between 1982 and 1995, 727 Stage I-II breast cancer patients were treated with breast conservation therapy at Massachusetts General Hospital. A retrospective analysis of the development of persistent arm edema was performed. Lymphedema was defined as a >2-cm difference in forearm circumference compared with the untreated side. The median follow-up was 72 months. Breast and regional nodal irradiation (BRNI) was administered in 32% of the cases and breast irradiation alone in 68%. RESULTS: Persistent arm lymphedema was documented in 21 patients. The 10-year actuarial incidence was 4.1%. The median time to edema was 39 months. The only significant risk factor for lymphedema was BRNI. The 10-year risk was 1.8% for breast irradiation alone vs. 8.9% for BRNI (p = 0.001). The extent of axillary dissection did not predict for lymphedema even within the subgroups of patients defined by the extent of irradiation. Most patients underwent Level I or II dissection. In this subgroup, the lymphedema risk at 10 years was 10.7% for BRNI vs. 1.0% for breast irradiation alone (p = 0.0003). CONCLUSION: Nodal irradiation was the only significant risk factor for arm lymphedema in patients receiving breast conservation therapy for early-stage breast cancer. Our data suggest that this risk is low with Level I/II dissection and breast irradiation. However, even after the addition of radiotherapy to the axilla and supraclavicular fossa, the development of lymphedema was only 1 in 10, lower than generally recognized.

[A case of large carcinoma of the tongue and mouth floor, in which chemotherapy using a combination of nedaplatin and 5-FU was effective].

We encountered a case of extensive squamous cell carcinoma ranging from the tongue to the mouth floor, in which chemotherapy using a combination of nedaplatin and 5-FU was effective. The patient was a 46-year-old male, who noticed a small mass in the mouth floor in September 2000, and visited the department of oral and maxillofacial surgery at a hospital on October 12, 2000. A 27 x 15 mm tumor with erosion was noted on the mouth floor, which was diagnosed as squamous cell carcinoma by biopsy, and the patient was referred to our department for treatment on November 16, 2000. Intra-oral findings included a healthy-colored induration with a bulge in the area ranging from the apex of the tongue posteriorly for 30 mm, and from the right lateral edge of the tongue to the left side exceeding the median area of the tongue by approximately 7 mm. MRI detected a tumor of approximately 2 cm in diameter in the area ranging from the median area of the tongue to the right ventral side of the tongue, which protruded on the mouth floor side. Two courses of combination chemotherapy using nedaplatin and 5-FU were performed. Nedaplatin (90 mg/m2, total 143 mg) and 5-FU (700 mg/m2, total 1,113 mg) were administered in a first course during December 15-19, 2000, and in the same amounts in a second course during January 23-27, 2001. Adverse effects of gastralgia and stomatitis occurred, but they gradually disappeared with time. The tumor with erosion in the tongue and mouth floor and induration disappeared 2 weeks after administration. Tongue was recovered, so that tongue movement was almost normal. Postoperative MR showed no abnormal signals in T2-weighed images, suggesting that the tumor in the right mouth floor had almost disappeared. External irradiation (40 Gy/20 times/28 days, 2 Gy/day, opposing bilateral portal irradiation) between March 13 and April 9, 2001, and micro-selection high dose fractionated interstitial irradiation (42 Gy/7 times/6 days, 6 Gy/1 time) April 18-23, 2001 were performed as booster therapy. Outpatient observation has shown a good clinical course without recurrence.

Neoadjuvant chemotherapy in multiple synchronous head and neck and esophagus squamous cell carcinomas.

A consecutive series of 22 patients with multiple synchronous squamous cell carcinomas of the upper aerodigestive tract was retrospectively reviewed. These patients were treated initially with cis-platinum combination chemotherapy before definitive locoregional therapy (surgery and/or radiation therapy). Sixteen of 21 patients had simultaneous head and neck and esophageal primaries, 3 patients had multiple synchronous head and neck primaries, 2 patients had head and neck (HN) and a bronchial epidermoid cancer, and 1 patient had simultaneous esophageal and bronchial carcinomas of epidermoid lineage. Sixteen (77%) of the 21 patients responded to chemotherapy in all the tumor sites evaluated, and a clinically complete response was obtained in 6 (29%). After definitive locoregional treatment, the complete local control rate was 68%, with 34 complete responses for 50 primary tumor sites in 21 patients. Twelve patients were free of disease after locoregional treatment. Six patients are still alive 27 to 57 months after complementary definitive locoregional treatment and a minimum follow-up of 27 months. Median survival for the overall group is 17 months. The response to chemotherapy is remarkable, which may be due to the small tumoral volume present in many of the cases (T1 to T2). Nevertheless, the present report stresses the importance of an aggressive combined therapeutic approach in this difficult clinical situation.

Analysis of treatment results in 36 children with retinoblastoma treated by scleral plaque irradiation.

This is a retrospective analysis of treatment results in 36 patients with retinoblastoma treated by the Radiation Oncology Department of Hahnemann University Hospital and the Division of Oncology of Wills Eye Hospital between January 1975 and December 1986. There were 14 females and 22 males; ages ranged from 2 months to 4 1/2 years of age at presentation. Leukocoria was the most common clinical sign of presentation. These patients were treated with external beam radiation therapy in combination with scleral plaque irradiation in 20 patients and with scleral plaque alone in 16 patients. Cobalt-60, Iodine-125, Iridium-192, and Ruthenium-106, scleral plaques were used. The dose delivered to the mid plane of the globe was 40 Gy and the scleral dose adjacent to the plaque was in the range of 180-200 Gy. The treatment was successful in 30 of 36 patients. Complications of radiation therapy were minimal in patients treated by scleral plaque alone. The advantages of this treatment modality are discussed.