Ariadne M. Bach

Weekly Trastuzumab and Paclitaxel Therapy for Metastatic Breast Cancer With Analysis of Efficacy by HER2 Immunophenotype and Gene Amplification

PURPOSE This phase II study evaluated weekly trastuzumab and paclitaxel therapy in women with HER2-normal and HER2-overexpressing metastatic breast cancer. Efficacy was correlated with immunohistochemical and fluorescent in situ hybridization (FISH) assay results. PATIENTS AND METHODS Eligible patients had bidimensionally measurable metastatic breast cancer. Up to three prior chemotherapy regimens, including prior anthracycline and taxane therapy, were allowed. Trastuzumab 4 mg/kg and paclitaxel 90 mg/m2 were administered on week 1, with trastuzumab 2 mg/kg and paclitaxel 90 mg/m2 administered on subsequent weeks. HER2 status was evaluated using four different immunohistochemical assays and FISH. RESULTS Patients received a median of 25 weekly infusions (range, one to 85 infusions). Median delivered paclitaxel dose-intensity was 82 mg/m2/wk (range, 52 to 90 mg/m2/wk). The intent-to-treat response rate for all 95 patients enrolled was 56.8% (95% confidence interval, 47% to 67%). A response rate of 61.4% (4.5% complete response, 56.8% partial response) was observed in 88 fully assessable patients. In patients with HER2-overexpressing tumors, overall response rates ranged from 67% to 81% compared with 41% to 46% in patients with HER2-normal expression (ranges reflect the different assay methods used to assess HER2 status). Differences in response rates between patients with HER2-overexpressing tumors and those with normal HER2 expression were statistically significant for all assay methods, with CB11 and TAB250 antibodies and FISH having the strongest significance. Therapy was generally well tolerated, although three patients had serious cardiac complications. CONCLUSION Weekly trastuzumab and paclitaxel therapy is active in women with metastatic breast cancer. Therapy was relatively well tolerated; however, attention to cardiac function is necessary.

Comparison of outcomes in elective partial vs radical nephrectomy for clear cell renal cell carcinoma of 4–7 cm

To compare the outcomes of patients who had a elective partial nephrectomy (PN) or radical nephrectomy (RN) for clear cell renal cell carcinoma (RCC) of 4–7 cm.

What is the yield of intraoperative ultrasonography during partial hepatectomy for malignant disease

BACKGROUND Previous studies have shown that intraoperative ultrasonography (IOUS) during hepatic resection for malignancy changes the operative plan or identifies occult unresectable disease in a large proportion of patients. This study was undertaken to reassess the yield of IOUS in light of recent improvements in preoperative staging. STUDY DESIGN Patients with potentially resectable primary or metastatic hepatic malignancies subjected to exploration, bimanual palpation of the liver, and IOUS were evaluated prospectively. Intraoperative findings were recorded, and preoperative imaging studies were reanalyzed by radiologists blinded to the intraoperative findings. The extent of disease based on preoperative imaging was compared with the intraoperative findings. RESULTS From October 1997 until November 1998, 111 patients were evaluated. At exploration, a total of 77 new findings or findings different than suggested on the imaging studies were identified in 61 patients (55%), the most common of which was additional hepatic tumors (n = 37). Thirty-five of 77 (45%) new findings were identified by IOUS alone and 10 (13%) by palpation alone; the remainder were identified by both palpation and IOUS. Forty-seven of 61 patients (77%) underwent a complete resection despite new intraoperative findings, with a modification (n = 28) or no change (n = 19) in the planned operation. Twenty-one patients (19%) had new findings identified only on IOUS. Thirteen of these patients underwent resection with no change in the operative plan, six underwent a modified resection and two were considered to have unresectable disease based solely on the findings of IOUS. CONCLUSIONS In patients with hepatic malignancies submitted to a potentially curative resection, new intraoperative findings or findings different than suggested on preoperative imaging studies are common. But resection with no change in the operative plan or a modified resection is still possible in the majority of patients despite such findings. The findings on IOUS alone rarely lead to a change in the operative plan.

Phase II Trial of Weekly Nanoparticle Albumin-Bound Paclitaxel With Carboplatin and Trastuzumab as First-line Therapy for Women With HER2-Overexpressing Metastatic Breast Cancer

PURPOSE This multicenter phase II trial evaluated the efficacy and safety of weekly nanoparticle albumin-bound paclitaxel with carboplatin and weekly trastuzumab as first-line therapy for women with HER2-overexpressing metastatic breast cancer (MBC). PATIENTS AND METHODS We treated 32 patients who had measurable MBC that was HER2-positive defined by an immunohistochemical staining score of 3+ or gene amplification by fluorescence in situ hybridization, required for those with an IHC of 2+. Patients were treated with albumin-bound paclitaxel 100 mg/m2 and carboplatin at area under the curve (AUC) = 2 on days 1, 8, and 15 of a 28-day cycle. Trastuzumab was administered at 2 mg/kg weekly after a loading dose of 4 mg/kg. Because of hypersensitivity reactions occurring during carboplatin infusion numbers 6-8 in 4 of the first 13 patients with this premedication-free regimen, the protocol was amended for carboplatin and dosed at AUC = 6 day 1 each 28-day cycle, in lieu of introducing steroid prophylaxis. Patients were treated with 6 cycles and allowed to continue with all 3 drugs or trastuzumab alone if free of progression and unacceptable toxicity after 6 cycles. RESULTS The overall response rate (ORR) was 62.5% (95% CI, 45.7%-79.3%) with 3 confirmed complete responders (CRs; 9%) and 17 confirmed partial responses (PRs; 53%). An additional 6 patients (19%) had stable disease (SD) for greater than 16 weeks for a clinical benefit rate (ORR + SD > 16 weeks) of 81%. As of April 16, 2009, 20 patients (63%) had progressed with a median progression-free survival (PFS) of 16.6 months (95% CI, 7.5-26.5 months). Antitumor activity was similar for patients treated with weekly carboplatin and every-4-week carboplatin (ORR, 65% vs. 67%, respectively). Hematologic toxicities were the only grade 4 toxicities noted and were infrequent with grade 4 neutropenia in 3 patients (9%) and 1 febrile neutropenia. Grade 2/3 peripheral neuropathy was uncommon (13%/3%). CONCLUSION Weekly albumin-bound paclitaxel with carboplatin and trastuzumab is highly active in HER2-overexpressing MBC. In the absence of corticosteroid premedication, which we avoided with albumin-bound paclitaxel, carboplatin seems best dosed every 4 weeks rather than weekly because of carboplatin-associated hypersensitivity reactions. The regimen was very well tolerated with few grade 3 and 4 nonhematologic toxicities experienced, and severe hematologic toxicity and peripheral neuropathy were infrequent.

Gallbladder cancer : Can ultrasonography evaluate extent of disease?

This study reviews the spectrum of sonographic findings in patients with gallbladder cancer, attempts to determine if sonography can identify patients with potentially resectable disease, and emphasizes the limitations of ultrasonography in the evaluation of ‐gallbladder cancer. Thirty‐five consecutive patients with histologically proven gallbladder carcinoma who had preoperative abdominal ultrasonography and surgery were identified. Involvement of the gallbladder and gallbladder fossa, metastases, bile ducts, portal vein, and adjacent lymph nodes was assessed sonographically. The extent of disease and staging as revealed by sonography was compared to operative and surgical pathologic findings. Masses in the gallbladder or gallbladder fossa were present at surgery in 26 patients; 22 (85%) of these masses were shown by sonography. Sonography identified six (67%) of nine cases of pathologically confirmed liver metastases, 11 (79%) of 14 cases of bile duct involvement, and two (67%) of three cases of portal venous involvement by tumor. Sonography revealed lymph node metastases in only five (36%) of 14 patients. None of the 12 cases with peritoneal metastases was identified sonographically. By surgical staging 16 (46%) patients had potentially resectable disease (stage III or less), and 19 (54%) patients had unresectable stage IV disease. Sonography correctly identified 15 (94%) of 16 patients with potentially resectable disease and seven (37%) of 19 patients with advanced disease. Twelve patients with advanced disease were under‐staged: nine had peritoneal metastases, two had liver metastases, and one had celiac adenopathy, which was not shown by sonography. In conclusion, sonography is reliable in the detection of a primary gallbladder mass or of local extension of tumor into the liver. However, sonographic findings do not accurately reflect the full extent of disease, and sonography is particularly limited in the diagnoses of metastases to the peritoneum and lymph nodes.

Metanephric adenoma of the kidney: clinical and radiological study of nine cases.

To analyse the clinical and radiological features of metanephric adenoma (MA, a rare benign renal tumour) in nine patients, and to review previous reports.

Natural History and Tumor Volume Kinetics of Papillary Thyroid Cancers During Active Surveillance

Importance Active surveillance of low-risk papillary thyroid cancer (PTC) is now an accepted alternative to immediate surgery, but experience with this approach outside of Japan is limited. The kinetics (probability, rate, and magnitude) of PTC tumor growth under active surveillance have not been well defined. Objective To describe the kinetics of PTC tumor growth during active surveillance. Design, Setting, and Participants Cohort study of 291 patients undergoing active surveillance for low-risk PTC (intrathyroidal tumors ⩽1.5 cm) with serial tumor measurements via ultrasonography at a tertiary referral center in the United States. Intervention Active surveillance. Main Outcomes and Measures The cumulative incidence, rate, and magnitude of the change in tumor diameter or volume, as well as associations with patient and tumor characteristics. Results Of the 291 patients, 219 (75.3%) were women; mean (SD) age was 52 (15) years. During a median (range) active surveillance of 25 (6-166) months, growth in tumor diameter of 3 mm or more was observed in 11 of 291 (3.8%) patients, with a cumulative incidence of 2.5% (2 years) and 12.1% (5 years). No regional or distant metastases developed during active surveillance. In all cases, 3-dimensional measurements of tumor volume allowed for earlier identification of growth (median, 8.2 months; range, 3-46 months before increase in tumor diameter). In multivariable analysis, both younger age at diagnosis (hazard ratio per year, 0.92; 95% CI, 0.87-0.98; P = .006) and risk category at presentation (hazard ratio for inappropriate, 55.17; 95% CI, 9.4-323.19; P < .001) were independently associated with the likelihood of tumor growth. Of the tumors experiencing volume growth, kinetics demonstrated a classic exponential growth pattern, with a median doubling time of 2.2 years (range, 0.5-4.8 years; median r2 = 0.75; range, 0.42-0.99). Conclusions and Relevance The rates of tumor growth during active surveillance in a US cohort with PTCs measuring 1.5 cm or less were low. Serial measurement of tumor volumes may facilitate early identification of tumors that will continue to grow and thereby inform the timing of surveillance imaging and therapeutic interventions.

Prospective Exploratory Analysis of the Association Between Tumor Response, Quality of Life, and Expenditures Among Patients Receiving Paclitaxel Monotherapy for Refractory Metastatic Breast Cancer

PURPOSE To prospectively evaluate the association between tumor response, change in quality of life (QoL), and hospital expenditures in patients with metastatic breast cancer (MBC) receiving single-agent paclitaxel. PATIENTS AND METHODS Eligible patients had bidimensionally measurable MBC and any number of previous therapies, excluding taxane chemotherapy. Paclitaxel was administered by various different infusion schedules. QoL measures were evaluated for each patient at baseline and serially using the Memorial Symptom Assessment Scale (MSAS)-Global Distress Index (GDI) and Functional Assessment of Cancer Therapy-Breast (FACT-B) instruments. Patients were assessed for early (first 6 weeks) and ever changes in QoL parameters. Charges were monitored through the hospitals centralized computer billing system and converted to cost ratios for the analysis. Correlations between response and improvement in QoL were assessed by Fishers exact test statistic. Associations between improvements in QoL with cost ratios were assessed by logistic regression and likewise between response and cost ratios. RESULTS Of the 59 patients treated, 50 had sufficient data for comparative analyses. The overall response rate was 24% (all partial responses). Minor responses were observed in 17% of patients, 25% had stable disease, and 29% had progression. Responding patients had significant improvement in QoL as assessed by MSAS-GDI (P =.004) and FACT-B (P =.028). The mean total cost/month ratios for patients experiencing improved GDI QoL scores was 1.31 versus 1.56 for those without QoL benefit (P =.52) and 1.05 versus 1.76 for responders versus nonresponders, respectively (P =.07). CONCLUSION Patients with evidence of tumor response on paclitaxel had a QoL benefit not observed in nonresponders, and this response was associated with a trend for lower overall costs.

The impact of tumour location on the histological subtype of renal cortical tumours

To determine whether the location of renal cortical tumours (RCTs) is a possible factor affecting tumour behaviour, by investigating whether exophytic vs a central location is associated with a difference in histological subtype distribution, as recognized prognostic factors for RCTs include size, stage, grade, and histological subtype.

Utility of Sonography for Small Hepatic Lesions Found on Computed Tomography in Patients With Cancer

Objective. To assess the performance of sonography in evaluating small indeterminate liver lesions detected on computed tomography in patients with cancer. Methods. Radiology database review from January 1, 1998, to August 4, 2000, identified 76 patients with 124 indeterminate hepatic lesions smaller than 1.5 cm on computed tomography who had abdominal sonography within 3 months. Sonographic reports and images were reviewed to assess whether lesions were referenced or specifically sought and to verify lesion correspondence, detection, and characterization. The validity of sonographic characterization was determined by histopathologic examination or follow‐up imaging (mean time to follow up, 17 months; range, 6.5–38.8 months). Results. Sixty (48%) of 124 indeterminate lesions were evident on sonography. Detection improved when lesions were specifically sought and lesion size was greater than 0.5 cm. Forty (66%) of 61 lesions were detected when the radiologist referenced the preceding computed tomography versus 20 (32%) of 63 lesions when the computed tomographic findings were not referenced (P = .0004). Fifty‐one (67%) of 76 lesions measuring 0.6 to 1.5 cm were detected on sonography versus 9 (19%) of 48 lesions measuring 0.1 to 0.5 cm. Lesion size (P < .0001) and body habitus (P = .02) were significant factors influencing lesion detection. Sonography characterized 56 (93%) of 60 detected lesions (33 cysts, 18 solid lesions/metastases, and 5 hemangiomas). Sonographic diagnoses were supported in 42 (93%) of 45 lesions by follow‐up imaging (37 of 40) or histopathologic examination (5 of 5). Conclusions. Sonography may be useful in cancer patients with average body habitus to characterize small (0.6‐ to 1.5‐cm) indeterminate liver lesions detected on computed tomography.