177 research outputs found
Pancreatic Head Mass from Metastatic Meningeal Hemangiopericytoma
Purpose. To illustrate the propensity of meningeal hemangiopericytoma
to spread extraneurally, as a distinction to the ordinary meningioma
3D-CT implanted interstitial brachytherapy for T2b nasopharyngeal carcinoma
<p>Abstract</p> <p>Background</p> <p>To compare the results of external beam radiotherapy in combination with 3D- computed tomography (CT)-implanted interstitial high dose rate brachytherapy (ERT/3D-HDR-BT) versus conventional external beam radiotherapy (ERT) for the treatment of stage T2b nasopharyngeal carcinoma (NPC).</p> <p>Methods</p> <p>Forty NPC patients diagnosed with stage T2b NPC were treated with ERT/3D-HDR-BT under local anesthesia. These patients received a mean dose of 60 Gy, followed by 12-20 Gy administered by 3D-HDR-BT. Another 101 patients diagnosed with non-metastatic T2b NPC received a mean dose of 68 Gy by ERT alone during the same period.</p> <p>Results</p> <p>Patients treated with ERT/3D-HDR-BT versus ERT alone exhibited an improvement in their 5-y local failure-free survival rate (97.5% vs. 80.2%, <it>P </it>= 0.012) and disease-free survival rate (92.5% vs. 73.3%, <it>P </it>= 0.014). Using multivariate analysis, administration of 3D-HDR-BT was found to be favorable for local control (<it>P </it>= 0.046) and was statistically significant for disease-free survival (<it>P </it>= 0.021). The incidence rate of acute and chronic complications between the two groups was also compared.</p> <p>Conclusions</p> <p>It is possible that the treatment modality enhances local control due to improved conformal dose distributions and the escalated radiation dose applied.</p
Outcomes following stereotactic radiosurgery or whole brain radiation therapy by molecular subtype of metastatic breast cancer
BACKGROUND: This study quantified clinical outcomes by molecular subtype of metastatic breast cancer (BC) following whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS). Doing so is important for patient counseling and to assess the potential benefit of combining targeted therapy and brain radiotherapy for certain molecular subtypes in ongoing trials.
MATERIALS AND METHODS: The National Cancer Database was queried for BC (invasive ductal carcinoma) cases receiving brain radiotherapy (divided into WBRT and SRS). Statistics included multivariable logistic regression to determine factors associated with SRS delivery, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling.
RESULTS: Of 1,112 patients, 186 (16.7%) received SRS and 926 (83.3%) underwent WBRT. Altogether, 410 (36.9%), 195 (17.5%), 162 (14.6%), and 345 (31.0%) were ER+/HER2-, ER+/HER2+, ER–/HER2+, and ER–/HER2–, respectively. In the respective molecular subtypes, the proportion of subjects who underwent SRS was 13.4%, 19.4%, 24.1%, and 15.7%. Respective OS for WBRT patients were 12.9, 22.8, 10.6, and 5.8 months; corresponding figures for the SRS cohort were 28.3, 40.7, 15.0, and 12.9 months (p < 0.05 for both). When comparing OS between treatment different histologic subtypes, patients with ER-/HER2+ and ER–/HER2– disease had worse OS than patients with ER+/HER2– disease, for both patients treated with SRS and for patients treated with WBRT.
CONCLUSIONS: Molecular subtype may be a useful prognostic marker to quantify survival following SRS/WBRT for metastatic BC. Patients with HER2-enriched and triple-negative disease had the poorest survival following brain irradiation, lending credence to ongoing studies testing the addition of targeted therapies for these subtypes
The alkylphospholipid, perifosine, radiosensitizes prostate cancer cells both in vitro and in vivo
The impact of HER2-directed targeted therapy on HER2-positive DCIS of the breast
BACKGROUND: In invasive breast cancer, HER2 is a well-established negative prognostic factor. However, its significance on the prognosis of ductal carcinoma in situ (DCIS) of the breast is unclear. As a result, the impact of HER2-directed therapy on HER2-positive DCIS is unknown and is currently the subject of ongoing clinical trials. In this study, we aim to determine the possible impact of HER2-directed targeted therapy on survival outcomes for HER2-positive DCIS patients.
MATERIALS AND METHODS: The National Cancer Data Base (NCDB) was used to retrieve patients with biopsy-proven DCIS diagnosed from 2004–2015. Patients were divided into two groups based on the adjuvant therapy they received: systemic HER2-directed targeted therapy or no systemic therapy. Statistics included multivariable logistic regression to determine factors predictive of receiving systemic therapy, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling to determine variables associated with OS.
RESULTS: Altogether, 1927 patients met inclusion criteria; 430 (22.3%) received HER2-directed targeted therapy; 1497 (77.7%) did not. Patients who received HER2-directed targeted therapy had a higher 5-year OS compared to patients that did not (97.7% vs. 95.8%, p = 0.043). This survival benefit remained on multivariable analysis. Factors associated with worse OS on multivariable analysis included Charlson-Deyo Comorbidity Score ≥ 2 and no receipt of hormonal therapy.
CONCLUSION: In this large study evaluating HER2-positive DCIS patients, the receipt of HER2-directed targeted therapy was associated with an improvement in OS. The results of currently ongoing clinical trials are needed to confirm this finding
ACR Appropriateness Criteria® Metastatic Epidural Spinal Cord Compression and Recurrent Spinal Metastasis
Metastatic epidural spinal cord compression (MESCC) is an oncologic emergency and if left untreated, permanent paralysis will ensue. The treatment of MESCC is governed by disease, patient, and treatment factors. Patient's preferences and goals of care are to be weighed into the treatment plan. Ideally, a patient with MESCC is evaluated by an interdisciplinary team promptly to determine the urgency of the clinical scenario. Treatment recommendations must take into consideration the risk-benefit profiles of surgical intervention and radiotherapy for the particular individual's circumstance, including neurologic status, performance status, extent of epidural disease, stability of the spine, extra-spinal disease status, and life expectancy. In patients with high spinal instability neoplastic score (SINS) or retropulsion of bone fragments in the spinal canal, surgical intervention should be strongly considered. The rate of development of motor deficits from spinal cord compression may be a prognostic factor for ultimate functional outcome, and should be taken into account when a treatment recommendation is made. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed every three years by a multidisciplinary expert panel. The guideline development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140123/1/jpm.2015.28999.sml.pd
ACR Appropriateness Criteria® Non-Spine Bone Metastases
Bone metastases are a common clinical problem, affecting many types of cancer patients. The presence of tumor in bone can cause significant morbidity including pain, neurological dysfunction, hypercalcemia, and pathological fracture leading to functional loss. The optimal treatment of a patient with bone metastases depends on many factors, including evaluation of the patient's goals of care, performance status, mechanical stability of the affected bone, life expectancy, and overall extent of disease. Treatment options may include radiotherapy, systemic therapies, surgical stabilization, medical pain management, and radiopharmaceuticals. Ideal management of bone metastases requires a coordinated multidisciplinary approach among diagnostic radiologists, radiation oncologists, medical oncologists, orthopedic surgeons, pain specialists, physiatrists, and palliative care specialists. The American College of Radiology Appropriateness Criteria? are evidence-based guidelines for specific clinical conditions that are reviewed every 3 years by a multidisciplinary expert panel. The guidelines development and review include an extensive analysis of current medical literature from peer-reviewed journals and the application of a well-established consensus methodology (modified Delphi) to rate the appropriateness of imaging and treatment procedures by the panel. In those instances where evidence is lacking or not definitive, expert opinion may be used to recommend imaging or treatment.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140118/1/jpm.2014.9395.pd
Transient bilateral abducens neuropathy with post-tetanic facilitation and acute hypokalemia associated with oxaliplatin: a case report
<p>Abstract</p> <p>Introduction</p> <p>Oxaliplatin is a cytotoxic platinum compound that is in widespread use in the treatment of gastrointestinal cancers. It has been occasionally associated with acute motor neuropathy, but the precise mechanism is uncertain. To the best of our knowledge, we report the first case of a patient demonstrating post-tetanic facilitation in the setting of transient bilateral abducens neuropathy and hypokalemia, after being infused with oxaliplatin.</p> <p>Case presentation</p> <p>A 47-year-old Indian woman with metastatic gastric cancer was receiving an oxaliplatin infusion at the initiation of her third cycle of palliative chemotherapy. She developed acute bilateral abducens neuropathy with post-tetanic facilitation alongside acute laryngopharyngodysesthesia and hypokalemia. Following supportive management, including potassium infusion and warming, her neurological signs and symptoms were spontaneously resolved. This syndrome did not recur in subsequent cycles following prolongation of infusion duration and the addition of supportive calcium and magnesium infusions.</p> <p>Conclusion</p> <p>The novel clinical observation of post-tetanic facilitation highlights a possible involvement of voltage-gated channels at the presynaptic terminals in the mechanism of acute oxaliplatin neurotoxicity.</p
Mutation signatures implicate aristolochic acid in bladder cancer development
10.1186/s13073-015-0161-3Genome Medicine71Article number 3
Assessing Matched Normal and Tumor Pairs in Next-Generation Sequencing Studies
Next generation sequencing technology has revolutionized the study of cancers. Through matched normal-tumor pairs, it is now possible to identify genome-wide germline and somatic mutations. The generation and analysis of the data requires rigorous quality checks and filtering, and the current analytical pipeline is constantly undergoing improvements. We noted however that in analyzing matched pairs, there is an implicit assumption that the sequenced data are matched, without any quality check such as those implemented in association studies. There are serious implications in this assumption as identification of germline and rare somatic variants depend on the normal sample being the matched pair. Using a genetics concept on measuring relatedness between individuals, we demonstrate that the matchedness of tumor pairs can be quantified and should be included as part of a quality protocol in analysis of sequenced data. Despite the mutation changes in cancer samples, matched tumor-normal pairs are still relatively similar in sequence compared to non-matched pairs. We demonstrate that the approach can be used to assess the mutation landscape between individuals
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