Setting Of Metastatic Disease Research Articles

Characterization of responders versus nonresponders to the anti-estrogen agent fulvestrant: A retrospective cohort study.

117 Background: Patients with breast cancer often benefit from targeted endocrine therapy with estrogen receptor antagonists. However, the duration of therapeutic response to these agents is variable. We investigated several clinical variables that may potentially affect the duration of response to fulvestrant in the setting of metastatic disease. Methods: A retrospective cohort analysis was done in 137 patients who received fulvestrant between 2000 and 2011 at Moll Cancer Center at Fairview Hospital and Cleveland Clinic Cancer Center. Several patient variables e.g. degree of estrogen receptor positivity, BMI etc. were analyzed. The RECIST 1.1 criteria was used to measure disease activity. Clinical benefit (i.e., responsiveness) was defined as complete response, partial response or stable disease at 24 weeks of therapy. 57 patients had clinical benefit whereas 80 did not. The clinical variables were then compared between the two groups using Chi square test, Fisher's exact test and Wilcoxon’s rank sum test. A multivariable logistic regression model was then used to assess the association. Results: Patients who were responders exhibited a significantly higher proportion of bone and/or soft tissue only metastases than non-responders (51% vs. 24 %, p= 0.001). They also appeared to be older (mean age ± SD: 64.1 ± 12.2 vs. 60.2 ± 13.2, p=0.044) and had prior aromatase inhibitor sensitiveness (83% vs. 56, p=0.006). However, in multivariate and logistic regression analyses, the site of metastases was found to be the only significant predictor of response. Patients with bone and/or soft tissue only metastases were more likely to be responders than patients with visceral metastases (OR= 2.883 [95 % CI= 1.313 - 6.328], P= 0.012; OR: 3.325 [95% CI, 1.600-6.908], p=0.001, respectively). Conclusions: In metastatic breast cancer, patients with bone and/or soft tissue only metastases were more likely respond to fulvestrant therapy than those with visceral metastases.

42IN - Tumor Markers and Biology in Pancreatic Cancer

ABSTRACT As we move forward into precision medicine, biomarkers will be required to define critical targets or to distinguish the diverse components of all cancers. Using biomarkers in therapeutic strategies has been very successful for many malignancies, especially breast cancer, lung cancer, and hematologic malignancies. Many barriers exist for similar applications in pancreatic ductal adenocarcinoma. First, the unusual aggressiveness of this malignancy overall, suggests that the diversity in this disease is constrained within a more narrow spectrum. Second, until recently, drug therapy has been only minimally effective in this disease. Finally, because so few patients proceed to resection and diagnosis is often made on scant fine-needle aspirates, access to tissue has been limited. However, this landscape is changing. Studies show that there are distinct metastatic patterns which may be governed by early genetic aberrations. In addition, genetic subclasses exist which, when evaluated in available human cell lines, also track with varying sensitivity to available chemotherapy. New chemotherapy combinations, albeit with more traditional cytotoxic drugs, are producing striking improvements in survival, even in the setting of metastatic disease. New and more successful treatments, such as FOLFIRINOX and selected gemcitabine combinations, provide more options and enlarge the playing field for the introduction of targeted therapeutics. This also brings the importance of clinically actionable biomarkers to the foreground. As this story unfolds, attention must be given to the importance of building biorepositories from primary and secondary tumor sites, with associated germline DNA and providing clinical annotation for the specimens. As technology improves and the cost of genomic sequencing decreases, we can expect a dramatic escalation in our understanding of the critical biologic pathways amenable to therapeutic intervention Disclosure The author has declared no conflicts of interest.

Should ACOSOG Z0011 change practice with respect to axillary lymph node dissection for a positive sentinel lymph node biopsy in breast cancer?

While any study can be criticized, the results of Z0011 clearly show that sentinel lymph node biopsy (SLNB) alone without axillary lymph node dissection (ALND) results in extremely low locoregional recurrence and excellent overall survival comparable to completion ALND. The observed results in this trial with SLNB alone were excellent. A prospective randomized study with results such as Z0011 should alter therapy. The skilled clinician must utilize his or her experience and the prospective randomized data of this study to improve patient care for women with breast cancer. On the other hand, ALND continues to be the standard of care for positive nodes in the axilla, with lymph node status as the most important prognostic indicator in overall survival (OS) and disease-free survival (DFS) in the management of early stage breast cancer. The advent of sentinel lymph node resection (SLNR) is challenging this notion. There is evidence to support the need for regional control of the axilla as a preventative means for locoregional recurrence and improvement in DFS. ALND is both a diagnostic and therapeutic approach that not only decreases rates of locoregional recurrence, but also guides further treatment strategies. Currently, there are no definable criteria that completely prevent patients from benefiting from ALND in the setting of metastatic disease to the axilla. It is, therefore, clear that ALND should be strongly considered in the management of the SLN-positive axilla. SLNR has its role in the management of early stage breast cancer, but whether SLNR alone should replace ALND is yet to be determined.

Primary systemic therapy in HER2-amplified breast cancer: a clinical review

Primary systemic therapy (PST) in early breast cancer is utilized in locally advanced breast tumors and when breast-conserving surgery is desirable. In addition, the PST setting provides an opportunity to monitor response including histopathological and biomarker examination of the tumor and host tissues before and after systemic therapy. Trastuzumab is a monoclonal antibody targeting the hEGF receptor that is overexpressed in 15–20% of breast tumors. Trastuzumab is effective in prolonging survival when used to treat women with hEGF receptor overexpressed tumors, both in adjuvant and metastatic disease settings. Trastuzumab has also shown promising activity in PST/neoadjuvant studies by achieving high rates of complete pathologic response. This is a review of clinical studies that incorporated trastuzumab in PST and/or neoadjuvant chemotherapy, including the results of recently reported studies using trastuzumab in combination with other novel therapies such as lapatinib or pertuzumab.

Early-phase trials compared to first- and second-line FDA-approved treatments in patients with advanced gallbladder cancer and cholangiocarcinoma.

e13020 Background: Patients with advanced cholangiocarcinoma (CC) and gallbladder carcinoma (GC) have few effective therapeutic options. We compared prognostic factors and clinical outcomes of CC/GC pts treated on phase I trials with that of their first-, second-line and last Food and Drug Administration (FDA)-approved therapy given in setting of metastatic disease. Methods: We retrospectively reviewed electronic medical records of patients with GC and CC evaluated in the phase I program clinic from November 2004 to March 2011. Results: Of the 72 patients with CC or GC, 32 (44%) were not enrolled on a trial mainly due to clinical deterioration (n=25). Of 40 treated patients (GC=6; CC=34; median age 60 years; median prior systemic therapies = 3), 8 (20%) had stable disease (SD) > 6 months; 3 (8%) achieved a partial response (PR); SD > 6 months/PR was observed mainly on protocols with hepatic arterial infusion drug administration and/or angiogenic inhibitors, anti-her2/neu agents or a novel MAPK/ERK kinase (MEK) inhibitor. Median progression-free survival (PFS) on phase I trials was 2.0 months (95% CI 1.7, 2.8) versus 3.0 months (95% CI 2.4, 5.0; p=0.95), 3.0 months (95% CI 2.3, 4.6; p=0.98), and 3.0 months (95% CI 2.4, 3.9; p=0.79) for their first-, second-, and last systemic therapy with FDA-approved agents given in the metastatic setting, respectively. In univariate analysis, factors associated with a shorter Phase I PFS were > 3 metastatic sites, elevated ALT (>56 IU/L), serum creatinine (>1.6mg/dL), and CA19-9 (>35U/mL). Conclusions: In heavily pretreated patients, PFS in the clinical trials setting remained poor but did not differ significantly from that of their first-line, second-line, and last prior therapy with FDA-approved agents. Response rate (SD >6 months/PR) of 28% was seen in trials with locoregional treatment or inhibitors of angiogenesis, her2/neu or MEK.

Limitations of preoperative biopsy in patients with metastatic renal cell carcinoma: comparison to surgical pathology in 405 cases

Study Type--Diagnostic (cohort) Level of Evidence: 2b. What's known on the subject? and What does the study add? Although there have been many investigations of biopsy for small renal masses, there are scant data on the accuracy of biopsy in the setting of metastatic renal cell carcinoma (mRCC). We report a large series of biopsies and compare with nephrectomy pathology in patients with mRCC. The present study highlights the inaccuracy of biopsy in the setting of metastatic disease, which is related to sampling error because of heterogeneity within the tumour and among metastases. These limitations are important to realize when designing trials that depend on pathological findings from biopsy and not nephrectomy. In addition, we found that biopsy of primary tumours were more likely than biopsy of metastatic sites to be diagnostic of RCC. Future studies with multiquadrant biopsies of primary tumours could yield the most accurate pathological results for future studies. • To evaluate the ability of preoperative biopsy to identify high-risk pathological features by comparing pathology from preoperative metastatic site and primary tumour biopsies with nephrectomy pathology in patients with metastatic renal cell carcinoma (mRCC). • We reviewed clinical and pathological data from patients who underwent biopsy before cytoreductive nephrectomy for mRCC at MD Anderson Cancer Center (MDACC) from 1991 to 2007. • Percutaneous biopsy techniques included fine-needle aspiration, core needle biopsy or a combination of both techniques. • The pathology of 405 preoperative biopsies (239 metastatic site, 166 primary tumour) from 378 patients was reviewed at MDACC before cytoreductive nephrectomy. • The biopsy and nephrectomy specimens had the same histological subtype in 96.0% of clear-cell renal cell carcinomas (RCCs) and 72.7% of non-clear-cell RCCs. • Of 76 nephrectomy specimens where sarcomatoid de-differentiation was identified, only seven (9.2%) were able to be identified from the preoperative biopsy. • In 38.3% of patients, the same Fuhrman grade was identified in both the biopsy and nephrectomy specimens. • A definitive diagnosis of RCC was more likely to be reported in primary tumour biopsies than in metastatic site biopsies. (P < 0.001). • Preoperative biopsy has limited ability to identify non-clear-cell histological subtype, Fuhrman grade or sarcomatoid features. • When surgical pathology is not available, a biopsy obtaining multiple samples from different sites within the primary tumour should be recommended rather than limited metastatic site biopsy to identify patients for clinical trials.

Abstract No. 372: Plasma-mediated radiofrequency coblation with subsequent stabilization in the setting of painful vertebral body metastatic disease

The interventional oncologist can have a significant impact on the quality of life of cancer patients through palliative pain management procedures. The utilization of advanced imaging and ablative techniques to control pain in cancer patients will be an important component of effective interventional oncology services as our subspecialty evolves. Specifically, the employment of plasma mediated radiofrequency energy to create cavities for subsequent stabilization in the setting of painful vertebral body metastatic disease is a viable, minimally invasive procedure for patients with otherwise limited options.

Lower Extremity Cutaneous Lesions as the Initial Presentation of Metastatic Adenocarcinoma of the Colon

Cutaneous metastases from colorectal cancers are rare and are usually present on the abdominal wall or previous surgical incision sites. Remote cutaneous lesions have been reported, however, often occur in the setting of widespread metastatic disease including other visceral secondaries. We present a case of lower extremity cutaneous metastases as the first sign of metastatic disease in a patient with adenocarcinoma of the colon. This case illustrates that new skin lesions may be the initial presentation of metastatic disease in a patient with a history of cancer.

P1-16-01: A Randomized, Double-Blinded, Controlled Study of Exemestane vs. Anastrozole for the First-Line Treatment of Postmenopausal Japanese Women with Hormone Receptor Positive Advanced Breast Cancer.

Abstract Background The steroidal irreversible aromatase inhibitor (AI) exemestane (E), the non-steroidal reversible AI anastrozole (A) and tamoxifen (T) are approved for the first-line treatment of the postmenopausal women with hormone receptor (HR) positive advanced breast cancer (ABC) in Japan. Although there are some studies which compare the efficacy and safety of AIs and T in the first-line disease setting, the number of studies that compare efficacy and safety of AIs is limited. We conducted this multicenter, randomized, double-blinded non-inferiority study, to evaluate the time to progression (TTP) in HR positive ABC randomized to therapy with E or A. Methods Patients (pts) who were ≥20 years [yrs], postmenopausal, ECOG PS ≤1 and had HR positive ABC that recurred after the adjuvant therapy or metastatic disease settings were eligible and randomized (1:1) to 25 mg/day of E or to 1 mg/day of A. Data were evaluated for non-inferiority of E compared to A defined as the upper limit of a two-sided 95% confidence interval (CI) of the hazard ratio (HR) of TTP being less than or equal to 1.25. The primary endpoint was TTP assessed by the independent radiological images review committee (RIRC). Secondary endpoints included TTP by investigator, time to treatment failure, overall survival (OS), objective response rate (ORR), clinical benefit rate, and safety. Results A total of 298 pts from 58 sites were randomized to E (n=149; mean age: 63.4 yrs) or A (n=149; mean age: 64.0 yrs). The mean BMI for the E and A arms were 23.0 kg/m2 and 23.6 kg/m2, respectively. Six pts (2 pts in E arm, 4 pts in A arm) were excluded from the full analysis set due to lack of evaluation for anti-tumor response after study medication started. Median TTP (as per RIRC) was 13.8 months (M) vs. 11.1 M for E vs. A, respectively (HR 1.007; 95% CI: 0.771−1.317). Median TTP (Investigator) was 13.8 M vs. 13.7 M for E vs. A, respectively (HR 1.059; 95% CI: 0.816−1.374). The median OS for A treated pts was 60.1 M, OS for E was not reached (as of data cut-off: December 8, 2010). ORR for E was 43.9% (95% CI: 35.3−52.8) and 39.1% (95% CI: 30.6−18.1) for A. Other analyses, including sub-population analyses are ongoing. The incidence of treatment related adverse events (AEs) in E arm was 71.1% (n=106) and in A arm 59.7% (n=89); the AEs were mostly grade 1 and 2 in 61.7% (n=92) and 53.7% (n=80) of pts respectively. They were expected and manageable. Treatment related SAEs were similar in both groups: 6 (4.0%) in E arm and 5 (3.4%) in A arm. The most common AEs for E were hot flushes (22.1%), arthralgias (16.8%), musculoskeletal stiffness (11.4%) and γ-GTP increased (10.1%); in A arm, hot flushes (14.8%) and arthralgia (16.8%) were observed in &amp;gt;10% pts. Conclusions Although median TTP (RIRC) of E is slightly improved compared with that of A, the result of TTP did not meet the non-inferiority criteria. There were no significant differences found between E and A in ORR. Although AEs in E were numerically higher, the observed AE profiles were similar to those previously reported for E and A. This study shows that E is comparable to A in efficacy and safety. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P1-16-01.

A single institution experience of streptozocin/fluorouracil combination chemotherapy: a case series

The combination chemotherapy regimen of streptozocin and 5-fluorouracil (FU/STZ) has been used for the treatment of metastatic neuroendocrine tumours. The aim of this study was to analyse the use of this regimen in a tertiary oncology referral centre over a 10-year period. We retrospectively analysed nine cases from February 2000 to May 2010. Patient demographics, chemotherapy schedule, toxicities, progression-free and overall survival were tabulated for each patient. The median progression-free survival was 17 months (range 3-48+ months), and overall survival 31 months (range 12-53+ months) with no toxicity related deaths. FU/STZ was a well-tolerated regimen that produced significant benefit in the setting of metastatic and progressive disease. Our case series demonstrated comparable progression-free survival and overall survival in relation to randomized controlled studies and previous case series.

Prognostic Clinicopathologic Factors in Longitudinally Followed Patients With Metastatic Small Bowel Carcinoid Tumors

Neuroendocrine tumors demonstrate heterogeneous behavior based on the site of origin and histology. This study aimed to delineate prognostic clinicopathologic features in patients with metastatic midgut carcinoid. All patients underwent resection of the primary tumor in the setting of metastatic disease. Survival was measured from the date of primary tumor resection and calculated by Kaplan-Meier estimation. Clinical data include age, sex, serum biomarkers, primary tumor size, Ki-67 index, and the performance of hepatic cytoreductive procedure. Serially collected serum biomarkers were considered as mean values within periods relative to primary resection: preoperative, 0 to 1 year postoperative, and years 1 to 5 postoperative. Log-rank comparisons were used to assess the prognostic value of the aforementioned features. Forty-nine patients (21 men) with metastatic midgut carcinoid who underwent primary tumor resection were identified. Median survival was 121 months. The overall 5-year survival rate was 83%. Age higher than 65 years (P = 0.01) and late postoperative chromogranin A (CgA; P = 0.02) were associated with decreased survival. This study highlights the favorable prognosis of patients with metastatic small bowel carcinoid in a multidisciplinary treatment program. Among other factors, elevated postoperative CgA is associated with decreased survival. The significance of increased CgA over time underlies the importance of longitudinal follow-up for these patients.

Disseminated Intravascular Coagulation with Excessive Fibrinolysis in Prostate Cancer: A Case Series and Review of the Literature

Objectives: To describe the clinical characteristics, diagnostic features, prognosis, and outcome of patients with prostate cancer and disseminated intravascular coagulation with excessive fibrinolysis (DIC XFL). Methods: We performed a retrospective analysis of prostate cancer patients seen at a single center from March 21, 2000, to July 31, 2006, with a fibrinogen level <150 mg/dl and two of the following criteria: platelets <150 × 10⁹/l, D-dimer >0.5 µg/ml, prothrombin time and activated partial thromboplastin time exceeding normal values, hemorrhage and/or thrombosis. Patients with comorbid conditions that cause coagulopathy were excluded. Results: Forty-two patients met the inclusion criteria. Most patients had high-grade prostate cancer (26% had Gleason 7 and 45% had Gleason 8–10). Three patients developed DIC XFL following surgery and 39 patients in the setting of metastatic disease; 93% were resistant to castration, and 50% had received prior taxanes. No deep-vein thromboses were documented. Management included blood transfusion, heparin, hormones, and chemotherapy. Median survival was 4 weeks. DIC XFL reversal was seen in 20% of metastatic patients, all of whom received new chemotherapy regimens. Median survival in this group was 26 weeks. Conclusions: DIC XFL is a rare complication of prostate cancer. Untreated, the risk of hemorrhage is high and the prognosis poor. Reversal of DIC XFL appears to correlate with response to new anticancer therapy.

Palliative Surgical Management of Patients with Unresectable Pancreatic Adenocarcinoma: Trends and Lessons Learned from a Large, Single Institution Experience

IntroductionRoutine palliative bypass has been advocated for palliation of patients with pancreatic adenocarcinoma who have inoperable disease discovered at the time of surgery. We examined trends in the relative use of palliative bypass over time with an emphasis on identifying changes in surgical indications, type of bypass performed, as well as perioperative outcomes associated with surgical palliation. MethodsBetween 1996 and 2010, 1,913 patients with pancreatic adenocarcinoma in the head of the pancreas were surgically explored. Data regarding preoperative symptoms, intraoperative findings, type of surgical procedure performed, as well as perioperative and long-term outcomes were collected and analyzed. ResultsOf the 1,913 patients, 583 (30.5%) underwent a palliative procedure. Most patients presented with jaundice (72.2%). The majority of patients were evaluated by CT scan (97.4%), which revealed a median tumor size of 3.2 cm. Most patients who underwent surgical palliation (64.5%) had a double bypass, while a minority had either gastrojejunostomy (28.2%) or hepaticojejunostomy (7.2%) alone. While the number of pancreaticoduodenectomies remained relatively stable over time, there was a temporal decrease in the utilization of palliative bypass (P < 0.001). Unanticipated locally advanced disease vs. liver/peritoneal metastasis as the indication for palliative surgery also changed over time (1996–2001: 47.8% vs. 52.2%; 2002–2007: 49.2% vs. 50.8%; 2008–2010: 17.2% vs. 82.7%) (P = 0.005). Palliative failure rates were 2.3% after hepaticojejunostomy and 3.1% after grastrojejunostomy. Patients with unsuspected metastatic disease had a worse survival compared with patients who had locally unresectable disease (median survival: 5 vs. 8 months, respectively; HR = 1.43, P = 0.001). ConclusionPalliative bypass procedures were less frequently performed over time, probably due to a significant decrease in the rate of unanticipated advanced locoregional disease at the time of exploration. While palliative bypass was effective, survival in the setting of metastatic disease was extremely short.

Adjuvant Chemotherapy in Colon Cancer: Ageism or Appropriate Care?

Adjuvant Chemotherapy in Colon Cancer: Ageism or Appropriate Care?

Biological Markers in Patients with Early-Stage Colon Cancer: Consensus and Controversies

Colorectal cancer is one of the most common malignancies in the Westernized world. Particularly in the setting of metastatic disease, advances in the use of biomarkers have resulted in “personalized therapy” being an aspect of routine care. However, their role is less clear-cut in the context of adjuvant treatment for early-stage colon cancer. We still largely rely on conventional TNM staging to determine prognosis and treatment options in early-stage disease. Ongoing research is elucidating alternative measures, in the form of prognostic and predictive biomarkers, which may better assist in understanding the wide spectrum of outcomes in early-stage disease; as well as the potential to select and tailor appropriate therapeutic options for an individual rather than simply treating a disease and a “cancer stage”. This review outlines key discoveries and controversies in the application of biomarkers to tailor treatment in early-stage colon cancer.

Safety and efficacy of single-agent adjuvant trastzumab in older women with breast cancer.

TPS109 Background: Trastuzumab is a humanized monoclonal antibody targeting the extracellular domain of the human epidermal growth factor receptor 2 (HER2) protein. The addition of trastuzumab to adjuvant chemotherapy, either concomitant or sequential, leads to better outcomes for women with HER2-positive breast cancer and in the setting of metastatic disease, single agent trastuzumab is effective and extremely well tolerated. The main adverse effect of trastuzumab is cardiotoxicity, which necessitated discontinuation prior to the planned one year of therapy in 17% of women on adjuvant trials. Since age is a risk factor for the cardiotoxicity of trastuzumab, and women ≥ 65 years were under-represented in trastuzumab clinical trials, determination of the safety and efficacy of trastuzumab in this patient population is lacking. This study is designed to define the risk-benefit profile of adjuvant single-agent trastuzumab in older women. Methods: This open label, single arm, multi-center, phase II study will include 124 women with stage I-III, HER2+ (defined as either 3+ by immunohistochemistry or gene amplified by fluorescent in situ hybridization), breast cancer who undergo primary surgery (mastectomy or lumpectomy) with at least a sentinel lymph node dissection, and are unwilling to undergo or are unable to tolerate adjuvant chemotherapy. Trastuzumab will be given, at 8mg/kg IV loading dose followed by 6mg/kg IV every three weeks, for 52 weeks. Patients will be followed prospectively for five years or until death, whichever comes first. The primary objective of the study is to evaluate the three-year cumulative incidence of cardiac events. Secondary objectives include i) the three-year cumulative incidence of asymptomatic decline in Left Ventricular Ejection Fraction; ii) the five-year cumulative incidence of cardiac events; iii) three-year disease-free and overall survival; iv) identification of correlative biomarkers of cardiac events (troponin-I, N-terminal brain natriuretic protein, and pro-inflammatory cytokines); and v) the longitudinal changes in Health-related Quality of Life, functional, cognitive, and mental status. Ten patients have been enrolled thus far.

The use of octreotide scans in the diagnosis and follow-up of neuroendocrine tumors (NETs).

e14631 Background: NETs are usually diagnosed and followed via a variety of imaging modalities, including MRI, CT scans and somatostatin scintigraphy (OctreoScan, SRS). SRS works by detecting somatostatin receptors found on NETs. There is ongoing debate as to which imaging modality should routinely be used to diagnose and follow patients affected with NETs. This project aims to determine if the information gathered from SRS corresponds or adds to results obtained from modern CT or MRI. Methods: We conducted a retrospective chart review by identifying all patients diagnosed with a NET who were seen at TOHCC between 2003-01-01 and 2009-03-31. We then identified all patients who underwent an SRS within 30 days of a CT or MRI. Results of the SRS were then compared against those of the latter imaging modalities. Results: 70 patients with a diagnosis of NET were identified. Of these, 28 had an SRS within 30 days of a CT or MRI. 5 patients had serial SRS plus either a CT or MRI within the defined time window. In total, 33 SRS results were allowed in the study. When compared to the results of the CT or MRI, 13 (39.4%) were true negatives (TN) SRS, 9 (33.3%) were true positives (TP), and 8 (24.3%) were false negatives (FN) in the setting of metastatic disease. The liver was the most common site missed. One patient had a false positive (FP) SRS (3.0%) with the location of the supposed lesion thought to be in the small bowel. Conclusions: The sensitivity of CT scans and MRIs is superior to that of SRS when investigating NET. There were no cases were an SRS identified lesions that were truly present but not seen on CT or MRI. The most common site missed by the SRS was the liver. This data suggest that SRS does not provide additional information and does not appear to be useful in the diagnosis and follow up of patients with NET, however, further research is needed.

Association of germ-line variation with platinum-based chemotherapy response in patients (pts) with urothelial carcinoma (UC).

4511 Background: Platinum-based therapy improves outcome in advanced UC, both in the neoadjuvant and metastatic disease setting. Since cell line and human studies in other cancers show associations...

The Use of High Dose Rate Brachytherapy Palliation after Failed Palliative External Beam Radiotherapy for a Cutaneous Malignant Melanoma of the Foot: A Case Report

While surgery is the mainstay of therapy for primary cutaneous melanoma, some very locally advanced lesions are either unresectable or the morbidity of resection is unacceptably high in the setting of metastatic disease. These types of primary melanomas must be addressed with alternative measures including chemotherapy, immunotherapy, radiotherapy, or a combination of the above. We treated a cutaneous lesion palliatively with high dose rate brachytherapy after having minimal tumor response to external beam radiation therapy. The tumor regressed after treatment, but a new lesion subsequently developed in its previous location. High dose rate brachytherapy may have a substantial impact on the management of cutaneous lesions, but further studies on its efficacy and toxicity must be evaluated.

Fatal Diffuse Alveolar Damage Associated with Oxaliplatin Administration

Oxaliplatin-based chemotherapy regimens are currently a standard of care for the treatment of colorectal cancer in both the adjuvant and metastatic disease settings. Significant improvements in survival have resulted from the use of oxaliplatin-based combinations. This article describes the use of oxaliplatin-based chemotherapy in a patient with stage III colon cancer who developed fatal diffuse alveolar damage during his adjuvant therapy. Other cases of pulmonary toxicity associated with oxaliplatin use are presented and the proposed pathophysiology of this rare occurrence is discussed.