Migration of Implanted Free Radioactive Seeds for Adenocarcinoma of the Prostate Using a Mick Applicator

Brachytherapy. 2004  |  Pubmed ID: 15374538

This study investigates the rate of free seed migration and associated seed-related sequelae after using a radioimmunoguided Mick applicator technique to place radioactive seeds within the prostate.

Breast Conservation Surgery Achieving>or=2 Mm Tumor-free Margins Results in Decreased Local-regional Recurrence Rates

The Breast Journal. Jan-Feb, 2006  |  Pubmed ID: 16409584

Whether cosmetically acceptable tumor-free (>/=2 mm) surgical margins reduce the local-regional recurrence risk for patients treated with fractionated radiation therapy, chemotherapy, and hormonal therapy is unknown. The benefit of a minimum cosmetically acceptable tumor-free margin remains speculative because no contemporary studies have investigated the extent of invasive disease infiltration within the breast beyond the primary tumor. To address these clinical issues, we conducted a retrospective study of 341 women diagnosed with stage I or II invasive breast cancer to determine the rate of local in-breast, elsewhere in-breast, and ipsilateral regional lymph node recurrences of breast cancer after conservation surgery achieving either tumor-free (>or=2 mm) or close (>0 mm to <2 mm) surgical margins followed by whole breast radiation therapy over a 6-year period from January 1996 to December 2002. Women may have received adjuvant chemotherapy or hormonal therapy as clinically indicated. After a median follow-up of 56 months from the completion of breast conservation surgery, 14 of the 341 women (4.1%) developed breast cancer recurrences. Crude ipsilateral recurrence rates were 1.8% (4 of 222) for tumor-free (>or=2 mm) versus 8.4% (10 of 119) for close (>0 mm to <2 mm) surgical margins (p=0.007). The estimated 5-year cumulative local recurrence rate was significantly less for women with tumor-free margins (2.1%) as compared to close surgical margins (8.9%) (p=0.004). Multivariate analyses identified negative estrogen receptor expression (p=0.004), close surgical margins (p=0.012), and the presence of angiolymphatic invasion (p=0.040) as prognostic factors for local-regional recurrences. Microscopically the extent of invasive disease infiltration beyond the primary tumor was on average 1 mm, with all measured invasive disease less than 1 cm. Based on our findings, cosmetically acceptable tumor-free (>or=2 mm) surgical margins significantly reduce local in-breast and regional lymph node recurrences with fractionated radiation therapy, chemotherapy, and hormonal therapy.

Intraoperative Electron Radiotherapy for Extremity Sarcomas Does Not Increase Acute or Late Morbidity

Clinical Orthopaedics and Related Research. May, 2006  |  Pubmed ID: 16467624

Intraoperative electron radiotherapy is used to treat surgical sites that potentially harbor occult tumor immediately after limb-sparing surgical resection of extremity soft tissue sarcomas. It is unknown whether single-fraction, high-dose intraoperative electron radiotherapy at the time of surgery increases wound morbidity when combined with preoperative or postoperative external beam radiotherapy. In a retrospective study, we evaluated whether intraoperative electron radiotherapy increased 90-day and late (> 90 days) wound complication rates by comparing patients who had adult extremity soft tissue sarcomas treated by limb-sparing surgery and preoperative (n = 14) or postoperative (n = 13) external beam radiotherapy. The median followup was 36 months. Seven (26%) patients had wound complications occurring within 90 days postoperatively and completion of radiotherapy. Late wound complication rates were similar. Two patients in each of the external beam radiotherapy groups required late subtotal limb amputations for prolonged wound complications. Our findings suggest intraoperative electron radiotherapy during limb-sparing surgery allows radiation dose escalation without increased 90-day or late-wound complication rates when combined with preoperative or postoperative external beam radiotherapy for patients with extremity soft tissue sarcomas. Level of Evidence: Prognostic Study, Level II (retrospective study). See the Guidelines for Authors for a complete description of levels of evidence.

Adjuvant Treatment and Survival in Obese Women with Endometrial Cancer: an International Collaborative Study

American Journal of Obstetrics and Gynecology. Jan, 2008  |  Pubmed ID: 18166317

The purpose of this study was to determine the impact of patient weight on the frequency of surgical staging lymphadenectomy and pelvic radiation. Adverse effects, disease relapse, and survival outcomes were investigated.

Comparison of Helical Tomotherapy Versus Conventional Radiation to Deliver Craniospinal Radiation

Technology in Cancer Research & Treatment. Jun, 2008  |  Pubmed ID: 18473494

The purpose of this study was to investigate whether helical tomotherapy would better dose-limit growing vertebral ring apophyses during craniospinal radiation as compared to conventional techniques. Four pediatric patients with M0 medulloblastoma received tomotherapy craniospinal radiation (23.4 Gy, 1.8 Gy/fx) by continuous helical delivery of 6 MV photons. Weekly blood counts were monitored. For comparison, conventional craniospinal radiation plans were generated. To assist in tomotherapy planning, a cross-sectional growth study of 52 children and young adults was completed to evaluate spine growth and maturation. Vertebral ring apophyses first fused along the posterolateral body-pedicle synostosis, proceeding circumferentially toward the anterior vertebral body such that the cervical and lumbar vertebrae fused early and mid-thoracic vertebrae fused late. For the four pediatric patients, tomotherapy resulted between 2% and 14% vertebral volume exceeding 23 Gy. Conventional craniospinal radiation predicted between 33% and 44% exceeding 23 Gy. Cumulative body radiation doses exceeding 4 Gy were between 50% and 57% for tomotherapy and between 25% and 37% for conventional craniospinal radiation. Tomotherapy radiation reduced neutrophil, platelet, and erythrocyte hemoglobin levels during treatment. Tomotherapy provides improved dose avoidance to growing vertebrae as compared to conventional craniospinal radiation. However, the long-term effects of tomotherapy dose avoidance on spine growth and large volume low dose radiation in children are not yet known.

Cyberknife Radiosurgery for Squamous Cell Carcinoma of Vulva After Prior Pelvic Radiation Therapy

Technology in Cancer Research & Treatment. Oct, 2008  |  Pubmed ID: 18783287

Limited options exist for patients experiencing a local recurrence of vulvar malignancies after surgery and pelvic radiation. These recurrences often are associated with cancer-related skin desquamation and poor clinical outcomes. A new radiotherapeutic treatment modality for the previously irradiated patient is cyberknife radiosurgery, which uses a linear accelerator mounted on an industrial robotic arm to allow non-coplanar radiation therapy delivery with sub-millimeter precision. This study describes the first reported use of cyberknife radiosurgery for the treatment of recurrent vulvar cancer in three women.

Chemotherapy Administration During Pelvic Radiation for Cervical Cancer Patients Aged >/=55 Years in the SEER-Medicare Population

Journal of Oncology. 2008  |  Pubmed ID: 19259335

Our study evaluated whether 1999 National Cancer Institute (NCI) chemoradiation guidelines for cervical cancer impacted treatment of women >/=55 years. We identified 385 women >/=55 years (median, 72 years) diagnosed with stage II-IVA cervical cancer between January, 1998 and December, 2002 in the United States Surveillance, Epidemiology, and End Results (SEER)-Medicare registries. Chemoradiation frequency tables were constructed for age, race, community setting, socioeconomic status, and comorbidity index. Of 385 women, 166 (43%) received chemoradiation as primary treatment. Prior to the 1999 NCI clinical alert, 5/43 (12%) in 1998 and 24/54 (44%) in 1999 received chemoradiation. The chemoradiation proportion was 41% (36/87) in 2000, 48% (51/107) in 2001, and 53% (50/94) in 2002 (trend, P < .01). Women >/=71 years had significantly lower odds of chemoradiation (P = .04). While SEER-Medicare data indicated an increasing trend for chemoradiation after the 1999 NCI clinical alert, chemoradiation was less frequent in elderly women with cervical cancer.

Radiation Therapy in Addition to Gross Total Resection of Retroperitoneal Sarcoma Results in Prolonged Survival: Results from a Single Institutional Study

Journal of Oncology. 2008  |  Pubmed ID: 19277103

Purpose. Typical treatment of retroperitoneal sarcomas (RPSs) is surgery with or without radiation therapy for localized disease. With surgery alone, local failure rates are as high as 90%; this led to radiation therapy playing an important role in the treatment of RPSs. Methods. Thirty-one patients with retroperitoneal sarcoma treated with gross total resection and radiation therapy make up this retrospective analysis. Nineteen were treated preoperatively and 12 postoperatively (median dose, 59.4 Gy)-sixteen also received intraoperative radiation therapy (IORT) (median dose, 11 Gy). Patients were followed with stringent regimens, including frequent CT scans of the chest, abdomen, and pelvis. Results. With a median follow-up of 19 months (range 1-66 months), the 2-year overall survival (OS) rate is 70% (median, 52 months). The 2-year locoregional control (LRC) rate is 77% (median, 61.6 months). The 2-year distant disease free survival (DDFS) rate is 70% (median not reached). There were no differences in radiation-related acute and late toxicities among patients treated pre- versus postoperatively, whether with or without IORT. Conclusions. Compared to surgery alone, neoadjuvant or adjuvant radiation therapy offers patients with RPS an excellent chance for long-term LRC, DDS, and OS. The integration of modern treatment planning for external beam radiation therapy and IORT allows for higher doses to be delivered with acceptable toxicities.

Radiation Therapy Compared with Pelvic Node Resection for Node-positive Vulvar Cancer: a Randomized Controlled Trial

Obstetrics and Gynecology. Sep, 2009  |  Pubmed ID: 19701032

To report long-term survival and toxicity of radiation compared with pelvic node resection for patients with groin node-positive vulvar cancer.

Stereotactic Body Radiosurgery for Pelvic Relapse of Gynecologic Malignancies

Technology in Cancer Research & Treatment. Oct, 2009  |  Pubmed ID: 19754216

Clinical management of pelvic relapses from gynecologic malignancies remains challenging. Bulky pelvic relapses often lead to symptomatic cancer-related complications and poor clinical outcomes. Options may be limited by prior surgical, chemotherapeutic, and radiation treatment. Stereotactic body radiosurgery is a novel treatment modality which allows high radiation dose delivery in a non-coplanar fashion with sub-millimeter precision utilizing a linear accelerator mounted on a robotic arm. This study details our clinical experience with stereotactic body radiosurgery for treatment of patients with pelvic relapses of gynecologic malignancies after prior pelvic radiation.

Retrospective Analysis of Concomitant Cisplatin During Radiation in Patients Aged 55 Years or Older for Treatment of Advanced Cervical Cancer: a Gynecologic Oncology Group Study

International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society. Oct, 2009  |  Pubmed ID: 19823064

Patients with stages II to IVa cervical cancer aged 55 years or older were compared with patients younger than 55 years who received weekly cisplatin during pelvic radiation for differences in chemoradiation administration, toxicity, and outcome.

Concurrent Cisplatin-based Chemoradiation International Federation of Gynecology and Obstetrics Stage IB2 Cervical Carcinoma

American Journal of Obstetrics and Gynecology. Feb, 2009  |  Pubmed ID: 19091305

The objective of the study was to assess the effectiveness of primary chemoradiation for stage IB(2) cervical carcinoma.

Modulating Radiation Resistance by Inhibiting Ribonucleotide Reductase in Cancers with Virally or Mutationally Silenced P53 Protein

Radiation Research. Dec, 2009  |  Pubmed ID: 19929413

Therapeutic ionizing radiation damages DNA, increasing p53-regulated ribonucleotide reductase (RNR) activity required for de novo synthesis of the deoxyribonucleotide triphosphates used during DNA repair. This study investigated the pharmacological inhibition of RNR in cells of virally or mutationally silenced p53 cancer cell lines using 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, Triapine(R), NSC #663249), a chemotherapeutic radiosensitizer that equally inhibits RNR M2 and p53R2 small subunits. The effects of 3-AP on RNR inhibition and resulting radiosensitization were evaluated in cervical (CaSki, HeLa and C33-a) and colon (RKO, RKO-E6) cancer cells. 3-AP treatment significantly enhanced radiation-related cytotoxicity in cervical and colon cancer cells. 3-AP treatment significantly decreased RNR activity, caused prolonged radiation-induced DNA damage, and resulted in an extended G(1)/S-phase cell cycle arrest in all cell lines. Similar effects were observed in both RKO and RKO-E6 cells, suggesting a p53-independent mechanism of radiosensitization. We conclude that inhibition of ribonucleotide reductase by 3-AP enhances radiation-mediated cytotoxicity independent of p53 regulation by impairing repair processes that rely on deoxyribonucleotide production, thereby substantially increasing the radiation sensitivity of human cancers.

Phase I Trial of Pelvic Radiation, Weekly Cisplatin, and 3-aminopyridine-2-carboxaldehyde Thiosemicarbazone (3-AP, NSC #663249) for Locally Advanced Cervical Cancer

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research. Feb, 2010  |  Pubmed ID: 20145183

This study assessed the safety/tolerability, pharmacokinetics, and clinical activity of three times weekly i.v. 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) in combination with once-weekly i.v. cisplatin and daily pelvic radiation in patients with gynecologic malignancies. 3-AP is a novel small-molecule inhibitor of ribonucleotide reductase (RNR) and is being tested as a potential radiosensitizer and chemosensitizer.

Posttherapy Residual Disease Associates with Long-term Survival After Chemoradiation for Bulky Stage 1B Cervical Carcinoma: a Gynecologic Oncology Group Study

American Journal of Obstetrics and Gynecology. Oct, 2010  |  Pubmed ID: 20541170

The objective of the study was to study posttherapy chemoradiation hysterectomy histology with long-term survival in bulky stage 1(B) cervical cancer patients.

Stage I, Grade 3 Endometrioid Adenocarcinoma of the Endometrium: an Analysis of Clinical Outcomes and Patterns of Recurrence

Gynecologic Oncology. Jan, 2010  |  Pubmed ID: 19875158

To study patterns of recurrence and survival outcomes in patients with surgical stage I, grade 3 endometrioid adenocarcinoma of the endometrium (EA) treated with various treatment modalities.

Ribonucleotide Reductase Inhibition Enhances Chemoradiosensitivity of Human Cervical Cancers

Radiation Research. Sep, 2010  |  Pubmed ID: 20831382

Abstract For repair of damaged DNA, cells increase de novo synthesis of deoxyribonucleotide triphosphates through the rate-limiting, p53-regulated ribonucleotide reductase (RNR) enzyme. In this study we investigated whether pharmacological inhibition of RNR by 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) enhanced chemoradiation sensitivity through a mechanism involving sustained DNA damage. RNR inactivation by 3-AP and resulting chemoradiosensitization were evaluated in human cervical (CaSki, C33-a) cancer cells through study of DNA damage (γ-H2AX signal) by flow cytometry, RNR subunit p53R2 and p21 protein steady-state levels by Western blot analysis and laser scanning imaging cytometry, and cell survival by colony formation assays. 3-AP treatment led to sustained radiation- and cisplatin-induced DNA damage (i.e. increased γ-H2AX signal) in both cell lines through a mechanism of inhibited RNR activity. Radiation, cisplatin and 3-AP exposure resulted in significantly elevated numbers and persistence of γ-H2AX foci that were associated with reduced clonogenic survival. DNA damage was associated with a rise in p53R2 but not p21 protein levels 6 h after treatment with radiation and/or cisplatin plus 3-AP. We conclude that blockage of RNR activity by 3-AP impairs DNA damage responses that rely on deoxyribonucleotide production and thereby may substantially increase chemoradiosensitivity of human cervical cancers.

Ribonucleotide Reductase Inhibition Enhances Chemoradiosensitivity of Human Cervical Cancers

Radiation Research. Nov, 2010  |  Pubmed ID: 20954859

For repair of damaged DNA, cells increase de novo synthesis of deoxyribonucleotide triphosphates through the rate-limiting, p53-regulated ribonucleotide reductase (RNR) enzyme. In this study we investigated whether pharmacological inhibition of RNR by 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) enhanced chemoradiation sensitivity through a mechanism involving sustained DNA damage. RNR inactivation by 3-AP and resulting chemoradiosensitization were evaluated in human cervical (CaSki, C33-a) cancer cells through study of DNA damage (γ-H2AX signal) by flow cytometry, RNR subunit p53R2 and p21 protein steady-state levels by Western blot analysis and laser scanning imaging cytometry, and cell survival by colony formation assays. 3-AP treatment led to sustained radiation- and cisplatin-induced DNA damage (i.e. increased γ-H2AX signal) in both cell lines through a mechanism of inhibited RNR activity. Radiation, cisplatin and 3-AP exposure resulted in significantly elevated numbers and persistence of γ-H2AX foci that were associated with reduced clonogenic survival. DNA damage was associated with a rise in p53R2 but not p21 protein levels 6 h after treatment with radiation and/or cisplatin plus 3-AP. We conclude that blockage of RNR activity by 3-AP impairs DNA damage responses that rely on deoxyribonucleotide production and thereby may substantially increase chemoradiosensitivity of human cervical cancers.

Low-dose Abdominal Radiation As a Docetaxel Chemosensitizer for Recurrent Epithelial Ovarian Cancer: a Phase I Study of the Gynecologic Oncology Group

Gynecologic Oncology. Feb, 2011  |  Pubmed ID: 21075438

The aim of this study was to determine the maximum tolerated dose and dose-limiting toxicity (DLT) of whole abdomen radiation as a chemosensitizer of weekly docetaxel for women with recurrent epithelial ovarian fallopian tube, or peritoneal cancers.

Low-dose-rate Brachytherapy for Treatment of Uterine Didelphys Malignancy

Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology. Feb, 2011  |  Pubmed ID: 21098325

Radiosensitization of Human Cervical Cancer Cells by Inhibiting Ribonucleotide Reductase: Enhanced Radiation Response at Low-dose Rates

International Journal of Radiation Oncology, Biology, Physics. Jul, 2011  |  Pubmed ID: 21470790

To test whether pharmacologic inhibition of ribonucleotide reductase (RNR) by 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) enhances radiation sensitivity during low-dose-rate ionizing radiation provided by a novel purpose-built iridium-192 cell irradiator.

Deoxynucleoside Salvage Facilitates DNA Repair During Ribonucleotide Reductase Blockade in Human Cervical Cancers

Radiation Research. Oct, 2011  |  Pubmed ID: 21756082

Cells generate 2'-deoxyribonucleoside triphosphates (dNTPs) for both replication and repair of damaged DNA predominantly through de novo reduction of intracellular ribonucleotides by ribonucleotide reductase (RNR). Cells can also salvage deoxynucleosides by deoxycytidine kinase/thymidine kinase 1 in the cytosol or by deoxyguanosine kinase/thymidine kinase 2 in mitochondria. In this study we investigated whether the salvage dNTP supply pathway facilitates DNA damage repair, promoting cell survival, when pharmacological inhibition of RNR by 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC no. 663249) impairs the de novo pathway. Human cervical cancer cells were subjected to radiation with or without 3-AP under medium deoxynucleoside concentrations of 0, 0.05, 0.5 and 5.0 µM. Efficacy of DNA damage repair was assessed by γ-H2AX flow cytometry and focus counts, by single cell electrophoresis (Comet assay), and by caspase 3 cleavage assay as a marker of treatment-induced apoptosis. Cell survival was assessed by colony formation. We found that deoxyribonucleotide salvage facilitates DNA repair during RNR inhibition by 3-AP and that salvage reduces the radiochemosensitivity of human cervical cancer cells.

18F-fluoro-2-deoxy-D-glucose Positron Emission Tomography Standard Uptake Value Ratio As an Indicator of Cervical Cancer Chemoradiation Therapeutic Response

International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society. Aug, 2011  |  Pubmed ID: 21792015

A ratio of 3 months of posttherapy to pretherapy 2-[F]fluoro-2-deoxy-d-glucose positron emission tomography with computed tomography (F-FDG PET/CT) standard uptake values (SUVs) predicts progression-free survival after chemoradiation in patients with stages IB2 to IVA cervical cancer.

Emerging Application of Stereotactic Body Radiation Therapy for Gynecologic Malignancies

Expert Review of Anticancer Therapy. Jul, 2011  |  Pubmed ID: 21806330

Stereotactic body radiation therapy (SBRT) involves delivery of image-guided, ablative radiation doses to planning treatment volume(s) using sophisticated dosimetric planning and target localization. Early on, clinical investigators pursued SBRT for the treatment of early stage non-small-cell lung cancer, lung and liver oligometastases and spinal metastases. As a result of its clinical efficacy in these disease sites, SBRT has been explored in the management of persistent or recurrent gynecological cancers. This article will consider indications for SBRT application in gynecological cancer management, will reflect on outcomes from key SBRT clinical trials and will discuss new therapeutic roles of SBRT for gynecological cancers.

Chemotherapy Plus Radiation in Advanced-stage Endometrial Cancer

International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society. Dec, 2011  |  Pubmed ID: 21897269

We hypothesize that adjuvant radiation and chemotherapy improve the clinical benefit from treatment of advanced-stage endometrial adenocarcinoma.

Adherence to Vaginal Dilation Following High Dose Rate Brachytherapy for Endometrial Cancer

International Journal of Radiation Oncology, Biology, Physics. Jul, 2011  |  Pubmed ID: 20619551

We report demographic, clinical, and psychosocial factors associated with adherence to vaginal dilation and describe the sexual and marital or nonmarital dyadic functioning of women following high dose rate (HDR) brachytherapy for endometrial cancer.

Robotic Surgery in Gynecologic Oncology

Obstetrics and Gynecology International. 2011  |  Pubmed ID: 22190946

Robotic surgery for the management of gynecologic cancers allows for minimally invasive surgical removal of cancer-bearing organs and tissues using sophisticated surgeon-manipulated, robotic surgical instrumentation. Early on, gynecologic oncologists recognized that minimally invasive surgery was associated with less surgical morbidity and that it shortened postoperative recovery. Now, robotic surgery represents an effective alternative to conventional laparotomy. Since its widespread adoption, minimally invasive surgery has become an option not only for the morbidly obese but for women with gynecologic malignancy where conventional laparotomy has been associated with significant morbidity. As such, this paper considers indications for robotic surgery, reflects on outcomes from initial robotic surgical outcomes data, reviews cost efficacy and implications in surgical training, and discusses new roles for robotic surgery in gynecologic cancer management.

On Model Ensemble Analyses of Nonmonotonic Data

Nucleosides, Nucleotides & Nucleic Acids. 2012  |  Pubmed ID: 22303993

Mammalian ribonucleotide reductase (RNR) activity has been reported to be nonmonotonic in ATP. If many nonlinear models are to be fitted to such data automatically as part of a model search process, use of the same initial parameter values across all models can lead to too many poor fitting, monotonic least squares fits, i.e., false model rejections. We propose that such fits can be rescued by using as initial parameter estimates the final estimates of neighboring models that do have nonmonotonic fits; here models are neighbors if complexes that they represent differ by at most one ligand. We use this approach to show that troughs in RNR activity versus ATP can be fitted similarly well by models that do or do not demand a third ATP binding site.

Management of 3-aminopyridine-2-carboxaldehyde Thiosemicarbazone-induced Methemoglobinemia

Future Oncology (London, England). Feb, 2012  |  Pubmed ID: 22335579

The anticancer agent 3-aminopyridine-2-carboxaldehyde thiosemicarbazone is a ribonucleotide reductase inhibitor. It inactivates ribonucleotide reductase by disrupting an iron-stabilized radical in ribonucleotide reductase's small subunits, M2 and M2b (p53R2). Unfortunately, 3-aminopyridine-2-carboxaldehyde thiosemicarbazone also alters iron II (Fe(2+)) in hemoglobin. This creates Fe(3+) methemoglobin that does not deliver oxygen. Fe(2+) in hemoglobin normally auto-oxidizes to inactive Fe(3+) methemoglobin at a rate of nearly 3% per day and this is counterbalanced by a reductase system that normally limits methemoglobin concentrations to less than 1% of hemoglobin. This balance may be perturbed by symptomatic toxicity levels during 3-aminopyridine-2-carboxaldehyde thiosemicarbazone therapy. Indications of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone sequelae attributable to methemoglobinemia include resting dyspnea, headaches and altered cognition. Management of methemoglobinemia includes supplemental oxygen, ascorbate and, most importantly, intravenously administered methylene blue as a therapeutic antidote.

Stereotactic Body Radiation Therapy for Nonresectable Tumors of the Pancreas

The Journal of Surgical Research. May, 2012  |  Pubmed ID: 21937061

Stereotactic body radiation therapy (SBRT) has emerged as a potential treatment option for local tumor control of primary malignancies of the pancreas. We report on our experience with SBRT in patients with pancreatic adenocarcinoma who were found not to be candidates for surgical resection.

A Phase I and Pharmacokinetic Study of Oral 3-aminopyridine-2-carboxaldehyde Thiosemicarbazone (3-AP, NSC #663249) in the Treatment of Advanced-stage Solid Cancers: a California Cancer Consortium Study

Cancer Chemotherapy and Pharmacology. Mar, 2012  |  Pubmed ID: 22105720

3-Aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP) is a novel small-molecule ribonucleotide reductase inhibitor. This study was designed to estimate the maximum tolerated dose (MTD) and oral bioavailability of 3-AP in patients with advanced-stage solid tumors.