H. Ashamalla

Acupuncture for the alleviation of hot flashes in men treated with androgen ablation therapy.

PURPOSE Hot flashes are common side effect due to androgen ablation therapy (AAT). The utility of acupuncture for hot flashes in men has not been thoroughly studied. We prospectively studied the effect of acupuncture in men with hot flashes. METHODS AND MATERIALS The study was approved by internal review board. Seventeen men with hot flashes and history of AAT for prostate cancer were enrolled. Three men declined participation before receiving any treatment. A hot flash score (HFS) was used to measure daily hot flashes. The composite daily score was calculated as the product of frequency × severity. The baseline daily scores were compared with scores taken at 2 and 6 weeks and at 8-month average follow-up. RESULTS No side effects were encountered during, immediately after treatment, or at 8 months. The mean initial HFS was 28.3; it dropped to 10.3 (p = 0.0001) at 2 weeks posttreatment, 7.5 (p = 0.0001) at 6 weeks, and 7.0 (p = 0.001) at 8 months. Clinical improvement for each patient is defined as the percent decrease in the mean HFS at each time point. The mean improvement at Weeks 2 and 6 was 68.4% (mean HFS decreased from 37.409 to 11.836, p = 0.001) and 89.2% (mean HFS decreased from 37.409 to 4.05, p = 0.0078) respectively. The improvement at 8 months was 80.3% (mean HFS decreased from 37.409 to 7.385, p = 0.002). CONCLUSIONS Acupuncture provides excellent control of hot flashes in men with a history of AAT. The absence of side effects and the durable response at 8 months are likely to be appealing to patients. Prospective randomized study is warranted to further evaluate this modality against medical therapy.

Radioactive gold grain implants in recurrent and locally advanced head-and-neck cancers

PURPOSE The radioactive gold grain applicator and seeds offer the flexibility necessary for effective use in the treatment of difficult sites of head-and-neck cancers. This study reviews our experience with gold grain (198Au) implants in locally advanced head-and-neck cancer to demonstrate their efficacy and feasibility. METHODS AND MATERIALS This study reviewed the charts of 94 patients who were treated with gold grain implants (1970-1995) and who were treated with radioactive 198Au implants. Thirty-seven of the subjects had implants located in the head-and-neck region, and these form the basis for this report. Of these, eight of the cases were located in the supraglottic larynx, five in the nasopharynx, four in the retromolar trigone, two in the oral cavity, four in the base of the tongue, four in the maxillary antrum, four in the palate, two in metastatic cervical lymph nodes (of unknown primary tumor), two in the tonsillar fossa, one in the pyriform fossa, and one in the posterior pharyngeal wall. Twenty-eight were recurrent cases after prior surgeries and radiation. Six were residual locally advanced cases, and 3 patients had their implants for a second primary tumor in an area that had been irradiated before. The gold grains were inserted with a Royal Marsden gun and 198Au, 130-180 MBq per seed. The median number of seeds implanted was 34. The total radiation dose, delivered at a margin of 0.5 cm around the target volume, ranged from 40 to 120 Gy, with a median of 80 Gy. RESULTS Complete local control was achieved in 33% and was contingent on two factors: (1) the size of the lesion implanted and (2) the histology and possible primary tumor site. In 19 tumors with a diameter greater than 2.5 cm, only 2 (11%) had complete tumor control. Conversely, 9 of 14 patients (64%) who had lesions smaller than 2.5 cm experienced successful local control (p = 0.002). Palatal-adenoid-cystic tumors had an average progression-free survival of 52 months, compared with 13, 9, and 4 months, respectively, in nasopharyngeal, oropharyngeal, and supraglottic squamous cell carcinoma. Palliation was successfully accomplished in 76% of the cases. Cessation of bleeding occurred in 50% of the subjects, pain control was achieved in 88%, and 60% experienced relief of dysphagia. CONCLUSIONS Gold grain implants have a role in the palliation of recurrent head-and-neck tumors, particularly for sites difficult to reach via other techniques, such as the supraglottic larynx, base of the tongue, hypopharynx, and the nasopharynx. Local control is best achieved in lesions less than 2.5 cm in dimension and is most successful in slow-growing tumors.

Hyperfractionated radiotherapy and paclitaxel for locally advanced/unresectable pancreatic cancer

PURPOSE To determine prospectively the maximal tolerated dose and potential antitumor activity of weekly paclitaxel with concurrent hyperfractionated radiotherapy in patients with locally advanced and/or unresectable pancreatic cancer. METHODS AND MATERIALS We embarked on Phase I-II study of hyperfractionated radiotherapy using a concomitant in-field boost to a total dose of 63.80 Gy in 6 weeks at 1.1 Gy/fraction. Paclitaxel was administered weekly on Days 1, 8, 15, 22, 29, and 36 as a 3-h infusion. Paclitaxel doses were escalated from 20 mg/m(2)/wk to 70 mg/m(2)/wk. Twenty patients were studied, 14 women and 6 men (mean age 64 years). Some patients presented with one or more symptoms. Obstructive jaundice was the main presenting symptom in 10 patients and epigastric pain in 14. All patients had unresectable histologically proven adenocarcinoma of the pancreas (15 head, 4 body, and 1 tail). Reasons for unresectability were involvement of the portal vein, and/or superior mesenteric artery (n = 14), paraaortic nodes (n = 8), and medically inoperable (n = 1). Fourteen patients underwent a biliary bypass procedure before treatment (four endoscopic stenting, five choledochojejunostomy, and five cholecystojejunostomy). The follow-up period ranged from 14 to 66 months (median 44). RESULTS The dose-limiting toxicity was observed at 70 mg/m(2)/wk. Grade IV Radiation Therapy Oncology Group late GI toxicity was seen in 1 patient in the form of duodenal stricture and hemorrhage. Grade II gastrointestinal adverse effects occurred in 13 patients and Grade 3 in 1 patient. No neurologic morbidity was encountered. Eight patients required cytokine support for Grade 2 and 3 neutropenia. The treatment course was delivered within the planned time in 80% of the patients. Complete relief of pain occurred in 10 of 14 patients. The CA 19-9 level was either stable or decreasing in 12 of 15 patients. Of 17 assessable patients, stable disease was seen in 10, regression in 2, a partial response in 3, and a complete response in 2. CONCLUSION The use of hyperfractionated radiotherapy to a dose of 63.80 Gy with concomitant weekly paclitaxel is tolerated. The maximal tolerated dose of paclitaxel for this study was 60 mg/m(2)/wk. The preliminary objective responses denote activity of the regimen. We recommend testing this regimen in larger scale studies.

Percutaneous tumor curettage and interstitial delivery of samarium-153 coupled with kyphoplasty for treatment of vertebral metastases.

OBJECT The object of this study was to investigate the use of a minimally invasive technique for treating metastatic tumors of the vertebral body, aimed at relieving pain, preventing further tumor growth, and minimizing the adverse effects of systemic use of samarium-153 ((153)Sm). METHODS The procedure is performed in the same fashion as a kyphoplasty, using a unilateral extrapedicular approach under local anesthesia/mild general sedation, with the patient in the lateral decubitus position. The tumor is accessed as in a standard kyphoplasty. The side is chosen according to the location of the metastasis. Prior to inflation of the balloon the tumor is debulked by percutaneous curettage. Balloon inflation is carried out as per standard kyphoplasty in an attempt to create a larger space and reduce a possible kyphotic deformity. Three mCi of (153)Sm-EDTMP (ethylenediaminetetramethylenephosphonic acid) is then mixed with bone cement (polymethylmethacrylate) and injected into the void created by the balloon tamp. RESULTS Twenty-four procedures were performed in 19 patients. There was reliable and reproducible delivery of the radiolabeled (153)Sm-EDTMP to the metastatic site, without spillage. The procedure was safe. There were no procedure-related complications. There was no hematological toxicity with the low doses of (153)Sm used. Pain improved in all patients. The long-term results related to tumor control continue to be investigated. CONCLUSIONS Combined percutaneous debulking of confined vertebral metastases and administration of local (153)Sm is feasible and safe. Furthermore, this technique leads to immediate relief of cancer-related pain and may help prevent or slow down the progression of vertebral metastatic tumors.

Phase I Trial of Vertebral Intracavitary Cement and Samarium (VICS): Novel Technique for Treatment of Painful Vertebral Metastasis

PURPOSE Kyphoplasty is an effective procedure to alleviate pain in vertebral metastases. However, it has no proven anticancer activity. Samarium-153-ethylene diamine tetramethylene phosphonate ((153)Sm-EDTMP) is used for palliative treatment of bone metastases. A standard dose of 1 mCi/kg is administrated intravenously. The present study was conducted to determine the feasibility of intravertebral administration of (153)Sm with kyphoplasty. METHODS AND MATERIALS A total of 33 procedures were performed in 26 patients. Of these 26 patients, 7 underwent procedures performed at two vertebral levels. The mean age of the cohort was 64 years (range, 33-86). The kyphoplasty procedure was performed using a known protocol; 1-4 mCi of (153)Sm was admixed with the bone cement and administered under tight radiation safety measures. Serial nuclear body scans were obtained. Pain assessment was evaluated using a visual analog pain score. RESULTS All patients tolerated the procedure well. No procedure-related morbidities were noted. No significant change had occurred in the blood counts at 1 month after the procedure. One case was not technically satisfactory. Nuclear scans revealed clear radiotracer uptake in the other 32 vertebrae injected. Except for the first patient, no radiation leakage was encountered. The mean pain score using the visual analog scale improved from 8.6 before to 2.8 after the procedure (p < .0001). Follow-up bone scans demonstrated a 43% decrease in the tracer uptake. CONCLUSION The results of our study have shown that the combination of intravertebral administration of (153)Sm and kyphoplasty is well tolerated with adequate pain control. No hematologic adverse effects were found. A reduction of the bone scan tracer uptake was observed in the injected vertebrae. Longer follow-up is needed to study the antineoplastic effect of the procedure.

Routine Histopathologic Characteristics Can Predict Oncotype DXTM Recurrence Score in Subsets of Breast Cancer Patients

This study assessed whether routine pathologic parameters could predict Oncotype DXTM recurrence score (RS) in 72 breast cancers diagnosed from 2008–2012. Comparing patients with low RS (0–17) vs. intermediate RS (18–30) vs. high RS (>30), the mean Nottingham score increased (5.5 vs. 6.3 vs. 7.2, respectively, p = .001) and the mean PR Allred score decreased (6.7 vs. 4.9 vs. 3.3, respectively, p = .001). A high RS was least likely for low-grade tumors (0% had high RS, p = .005), and strong PR positivity (9% had high RS, p = .017). A low RS was least likely for cancers that were both high grade and PR weak/negative.

Mutant p53 and the response to chemotherapy and radiation.

In addition to playing roles in the genesis and progression of cancer, mutant p53 also appears to play a significant role in the response to cancer therapy. In response to chemotherapy and radiation, two mainstays of cancer treatment, most cancer cells harboring p53 mutations show a reduced sensitivity compared to cells lacking p53 or those with wild type p53. However, there are also many instances where mutant p53 has shown no effect or enhances cellular sensitivity to chemotherapy and radiation. Similar to the in vitro cellular studies, the majority of clinical studies show a correlation between the presence of mutant p53 in patient tumors and adverse outcomes following treatment with chemotherapy agents or radiation in comparison to tumors with wild-type p53. However, it still remains unclear whether the presence of mutant p53 in tumors can serve as a reliable prognostic factor and aid in treatment planning. Thus, as genomic analysis of patient tumors becomes more cost effective, the role of mutant p53 in tumor responses from cancer therapy ultimately needs to be addressed. This chapter will discuss current mechanisms of how p53 mutations affect cellular responses to chemotherapy and radiation and discuss patient outcomes based on p53 status.

Model-guided therapy for hepatocellular carcinoma: a role for information technology in predictive, preventive and personalized medicine

Predictive, preventive and personalized medicine (PPPM) may have the potential to eventually improve the nature of health care delivery. However, the tools required for a practical and comprehensive form of PPPM that is capable of handling the vast amounts of medical information that is currently available are currently lacking. This article reviews a rationale and method for combining and integrating diagnostic and therapeutic management with information technology (IT), in a manner that supports patients through their continuum of care. It is imperative that any program devised to explore and develop personalized health care delivery must be firmly rooted in clinically confirmed and accepted principles and technologies. Therefore, a use case, relating to hepatocellular carcinoma (HCC), was developed. The approach to the management of medical information we have taken is based on model theory and seeks to implement a form of model-guided therapy (MGT) that can be used as a decision support system in the treatment of patients with HCC. The IT structures to be utilized in MGT include a therapy imaging and model management system (TIMMS) and a digital patient model (DPM). The system that we propose will utilize patient modeling techniques to generate valid DPMs (which factor in age, physiologic condition, disease and co-morbidities, genetics, biomarkers and responses to previous treatments). We may, then, be able to develop a statistically valid methodology, on an individual basis, to predict certain diseases or conditions, to predict certain treatment outcomes, to prevent certain diseases or complications and to develop treatment regimens that are personalized for that particular patient. An IT system for predictive, preventive and personalized medicine (ITS-PM) for HCC is presented to provide a comprehensive system to provide unified access to general medical and patient-specific information for medical researchers and health care providers from different disciplines including hepatologists, gastroenterologists, medical and surgical oncologists, liver transplant teams, interventional radiologists and radiation oncologists. The article concludes with a review providing an outlook and recommendations for the application of MGT to enhance the medical management of HCC through PPPM.

Perianal Paget disease treated definitively with radiotherapy

Extramammary Paget disease (empd) is a relatively rare cutaneous disorder described as an apocrine gland tumour occurring in both a benign and a malignant form with metastatic potential. The areas of the body affected are the vulva, perianal region, penis, scrotum, perineum, and axilla, all of which contain apocrine glands. When empd affects the perianal region, it is called perianal Paget disease (ppd). All forms of empd, including ppd, are typically treated by wide surgical excision. Perianal Paget disease usually occurs later in life in patients who are often poor surgical candidates, but the available literature is scarce regarding other treatment modalities, including definitive radiotherapy. We contend that ppd can be safely and effectively treated with radiotherapy, and here, we present the case of a 75-year-old woman with ppd who was successfully so treated. A brief review of the literature concerning the diagnosis, natural history, and treatment of ppd is also included.

Commissioning and clinical results utilizing the Gildenberg-Laitinen Adapter Device for X-ray in fractionated stereotactic radiotherapy

BACKGROUND The Gildenberg-Laitinen Adapter Device for X-Ray (GLAD-X/LS) frame is a positioning device that allows the use of the same fiducial points as the Brown-Robert-Wells (BRW) system. Thus it permits treatment planning to be accomplished by the Radionics X-knife Radiosurgery Program. We investigated the commissioning and clinical benefits of the GLAD-X/LS for fractionated stereotactic radiotherapy (FSRT) in patients who were unable to tolerate the Gill-Thomas-Cosman (GTC) frame. METHODS AND MATERIALS Commissioning of the GLAD-X/LS system was done via use of a Rando Phantom. A target volume of 2 x 2 x 2 cm was drilled into the phantom head. An ion chamber and thermoluminescence dosimetric chips (TLDs) were implanted in the target. A simulated treatment course consisting of 5 stereotactic radiotherapy fractions (300 cGy, 30 mm collimator) was delivered to the phantom head. A total of 27 patients who could not tolerate the GTC frame were treated using the GLAD-X/LS system. A total of 35 isocenters were used; the median number of treatment fractions was eight. Reproducibility of the x, y, and z coordinates was examined and correlated to the same determined using orthogonal port films. Relocation accuracy and reproducibility were further assessed comparing the x, y, and z coordinates of the target center with multiplanar reconstructed coronal and sagittal images. Patient tolerance of the device was also evaluated daily throughout the treatment. RESULTS The measured TLD and ion chamber doses were within 3% of the prescribed dose at the isocenter. The same dose accuracy was also found at incremental distances of 5 mm, 10 mm, and 15 mm from the isocenter. All patients tolerated the treatment and the device well. Six patients experienced mild ear canal pain, and softer or smaller earpieces were substituted. The mean relocation accuracy was 1.5 mm +/- 0.8. CONCLUSIONS The GLAD-X/LS system has excellent accuracy and reproducibility with the mean relocation accuracy of 1.5 mm +/- 0.8. The device is well-tolerated by patients, with no significant complications. Larger scale studies are necessary before routine use can be recommended for the administration of FSRT.