Is Neoadjuvant Therapy Sufficient in Resected Pancreatic Cancer Patients? A National Study

Background

Despite the increasing use of neoadjuvant treatment, the question of whether preoperatively treated, successfully resected patients should receive additional postoperative adjuvant treatment remains unanswered. We evaluate the impact of adjuvant therapy following neoadjuvant treatment and pancreatectomy in pancreatic cancer patients in a large national study.

Methods

We used the National Cancer Data Base between 2006 and 2013 to identify resected, non-metastatic pancreatic adenocarcinoma patients who received neoadjuvant chemo(radio)therapy followed by pancreatectomy. Kaplan-Meier and multivariate Cox proportional hazard regression analyses were performed to compare survival between groups.

Results

In total, 1357 patients were identified. Of the patients, 38.6% (n = 524) were treated with postoperative therapy. There was no difference in unadjusted median overall survival between patients who did and did not receive postoperative therapy (median survival, 27.5 vs. 27.1 months, log-rank p = 0.5409). Postoperative therapy was not significantly associated with favorable prognosis in patients with positive resection margins (log-rank p = 0.6452) or positive lymph nodes (log-rank p = 0.6252). On multivariate analysis, receipt of postoperative therapy was not predictive of survival (hazard ratio 0.972; 95% CI 0.848–1.115; p = 0.6876).

Conclusions

Our results using national data suggest that after receipt of neoadjuvant therapy and pancreatectomy, additional postoperative therapy may not provide additional survival benefit. These data warrant further prospective data collection and consideration for clinical trials.

     

Big Data and Total Hip Arthroplasty: How Do Large Databases Compare?

Background

Use of large databases for orthopedic research has become extremely popular in recent years. Each database varies in the methods used to capture data and the population it represents. The purpose of this study was to evaluate how these databases differed in reported demographics, comorbidities, and postoperative complications for primary total hip arthroplasty (THA) patients.

Is Reporting of Recurrence Data Important in Pancreatic Cancer?

Background: Therapeutic approaches to patients with pancreatic cancer have undergone a paradigm shift in recent years. However, little is known about the outcome of patients with recurrent pancreatic cancer who undergo treatment. The purpose of this study was to identify patients with recurrent pancreatic cancer and to determine whether treatment after recurrence had any effect on outcome.Methods: A review of all patients undergoing surgical resection with curative intent revealed 70 patients with documented recurrence and complete medical records. Patients were grouped into three categories: group 1 included those who received treatment after recurrence (n = 45), group 2 included those who were not offered treatment (n = 9), and group 3 included those with poor performance status who received no treatment (n = 16).Results: The median overall survival for the three groups was 26, 18, and 14.5 months for groups 1, 2, and 3, respectively (P < .00001). The median survival after recurrence was 10 months, 6 months, and 1 month, respectively, for the three groups (P < .0001).Conclusions: This is the first series we are aware of that compares the outcomes of patients who received treatment after recurrence of pancreatic cancer with the outcomes of those who received no treatment. In this series, it seems that patients who were well enough to tolerate additional therapy had a longer survival than those who received supportive care only. This may be important in the analysis of adjuvant therapy trials of pancreatic cancer with survival as an end point.     

PSA-based Screening for Prostate Cancer: How Does It Compare with Other Cancer Screening Tests?

CONTEXT: Despite the substantive societal impact of prostate cancer, the medical community is currently divided on the balance between benefit and harm of screening for prostate cancer using prostate-specific antigen (PSA). OBJECTIVE: To examine whether PSA-based screening for prostate cancer meets current guidelines on efficacy and effectiveness for screening, and how it compares with other currently implemented cancer-screening methods. EVIDENCE ACQUISITION: A literature search was conducted for reviews and individual studies that have examined the performance of screening for colorectal, cervical, breast, and prostate cancer. Each screening method was assessed using the United Kingdom National Screening Committee guidelines. Data on screening test performance (sensitivity, specificity, etc) were extracted from these articles for comparison. EVIDENCE SYNTHESIS: In common with other cancers for which screening is conducted, prostate cancer represents a significant morbidity and mortality burden. The PSA test can be considered "simple" and "safe" within appropriate boundaries. The sensitivity/specificity profile of PSA is not optimal but has clinical validity: Cases missed at screening detected as interval cases do not have a poor outcome. Early prostate cancer intervention can be beneficial for long-term outcomes, although the benefits need to be weighed against the adverse effects of intervention. Early evidence from screening studies also suggests positive stage and grade shifts, although Level 1 mortality data are still awaited. Robust cost-effectiveness data are still lacking, although current evidence suggests that PSA screening may lie within acceptable limits. CONCLUSION: Until better markers become available, PSA can be regarded as an appropriate screening tool for prostate cancer at a population level.     

Systemic Therapy for Resected Pancreatic Adenocarcinoma: How Much is Enough?

Annals of Surgical Oncology - Systemic therapy is an essential part of treatment for pancreatic ductal adenocarcinoma (PDAC). However, not all patients receive every cycle of chemotherapy and even...     

Does the Mechanism of Lymph Node Invasion Affect Survival in Patients with Pancreatic Ductal Adenocarcinoma?

Background  

Lymph node metastases are prognostically significant in pancreatic ductal adenocarcinoma. Little is known about the significance of direct lymph node invasion.     

Do Tumor Cavitation and Sex in Resected Stage I Non-Small-Cell Lung Cancer Correlate with Prognosis?

Background  Multiple factors have been reported as affecting the prognosis, and they affect the therapeutic outcomes of stage I non-small-cell lung cancer (NSCLC) patients. Most studies focus on patients receiving combined-modality therapy, whereas there are few studies that focus on patients undergoing surgery alone. The aim of this study was to identify risk factors for disease relapse and unfavorable prognosis in stage I NSCLC patients treated with surgery alone. Methods  A total of 315 stage I NSCLC patients who were treated with surgery alone as the definitive therapy were identified. Risk factors for disease relapse and unfavorable prognosis were estimated by univariate and multivariate analyses. Results  Sex, tumor pathologic stage, and cavitating lung cancer were identified as independent risk factors for relapse and overall survival using the multivariate analysis. Sex, tumor pathologic stage, and cavitating lung cancer were identified as independent risk factors for early relapse, and sex and cavitating lung cancer were independent risk factors for late relapse. Conclusion  Tumor cavitation, pathologic stage IB, and being male are predictors of poor outcome for patients with stage I NSCLC who undergo resection.     

How Are Indeterminate Pulmonary Nodules at Diagnosis Associated with Survival in Patients with High-Grade Osteosarcoma?

BackgroundPulmonary metastases are a poor prognostic factor in patients with osteosarcoma; however, the clinical significance of subcentimeter lung nodules and whether they represent a tumor is not fully known. Because the clinician is faced with decisions regarding biopsy, resection, or observation of lung nodules and the potential impact they have on decisions about resection of the primary tumor, this remains an area of uncertainty in patient treatment. Surgical management of the primary tumor is tailored to prognosis, and it is unclear how aggressively patients with indeterminate pulmonary nodules (IPNs), defined as nodules smaller than 1 cm at presentation, should be treated. There is a clear need to better understand the clinical importance of these nodules.Questions/purposes(1) What percentage of patients with high-grade osteosarcoma and spindle cell sarcoma of bone have IPNs at diagnosis? (2) Are IPNs at diagnosis associated with worse metastasis-free and overall survival? (3) Are there any clinical or radiologic factors associated with worse overall survival in patients with IPN?MethodsBetween 2008 and 2016, 484 patients with a first presentation of osteosarcoma or spindle cell sarcoma of bone were retrospectively identified from an institutional database. Patients with the following were excluded: treatment at another institution (6%, 27 of 484), death related to complications of neoadjuvant chemotherapy (1%, 3 of 484), Grade 1 or 2 on final pathology (4%, 21 of 484) and lack of staging chest CT available for review (0.4%, 2 of 484). All patients with abnormalities on their staging chest CT underwent imaging re-review by a senior radiology consultant and were divided into three groups for comparison: no metastases (70%, 302 of 431), IPN (16%, 68 of 431), and metastases (14%, 61 of 431) at the time of diagnosis. A random subset of CT scans was reviewed by a senior radiology registrar and there was very good agreement between the two reviewers (κ = 0.88). Demographic and oncologic variables as well as treatment details and clinical course were gleaned from a longitudinally maintained institutional database. The three groups did not differ with regard to age, gender, subtype, presence of pathological fracture, tumor site, or chemotherapy-induced necrosis. They differed according to local control strategy and tumor size, with a larger proportion of patients in the metastases group presenting with larger tumor size and undergoing nonoperative treatment. There was no differential loss to follow-up among the three groups. Two percent (6 of 302) of patients with no metastases, no patients with IPN, and 2% (1 of 61) of patients with metastases were lost to follow-up at 1 year postdiagnosis but were not known to have died. Individual treatment decisions were determined as part of a multidisciplinary conference, but in general, patients without obvious metastases received (neo)adjuvant chemotherapy and surgical resection for local control. Patients in the no metastases and IPN groups did not differ in local control strategy. For patients in the IPN group, staging CT images were inspected for IPN characteristics including number, distribution, size, location, presence of mineralization, and shape. Subsequent chest CT images were examined by the same radiologist to reevaluate known nodules for interval change in size and to identify the presence of new nodules. A random subset of chest CT scans were re-reviewed by a senior radiology resident (κ = 0.62). The association of demographic and oncologic variables with metastasis-free and overall survival was first explored using the Kaplan-Meier method (log-rank test) in univariable analyses. All variables that were statistically significant (p < 0.05) in univariable analyses were entered into Cox regression multivariable analyses.ResultsFollowing re-review of staging chest CTs, IPNs were found in 16% (68 of 431) of patients, while an additional 14% (61 of 431) of patients had lung metastases (parenchymal nodules 10 mm or larger). After controlling for potential confounding variables like local control strategy, tumor size, and chemotherapy-induced necrosis, we found that the presence of an IPN was associated with worse overall survival and a higher incidence of metastases (hazard ratio 1.9 [95% CI 1.3 to 2.8]; p = 0.001 and HR 3.6 [95% CI 2.5 to 5.2]; p < 0.001, respectively). Two-year overall survival for patients with no metastases, IPN, or metastases was 83% [95% CI 78 to 87], 65% [95% CI 52 to 75] and 45% [95% CI 32 to 57], respectively (p = 0.001). In 74% (50 of 68) of patients with IPNs, it became apparent that they were true metastatic lesions at a median of 5.3 months. Eighty-six percent (43 of 50) of these patients had disease progression by 2 years after diagnosis. In multivariable analysis, local control strategy and tumor subtype correlated with overall survival for patients with IPNs. Patients who were treated nonoperatively and who had a secondary sarcoma had worse outcomes (HR 3.6 [95% CI 1.5 to 8.3]; p = 0.003 and HR 3.4 [95% CI 1.1 to 10.0]; p = 0.03). The presence of nodule mineralization was associated with improved overall survival in the univariable analysis (87% [95% CI 39 to 98] versus 57% [95% CI 43 to 69]; p = 0.008), however, because we could not control for other factors in a multivariable analysis, the relationship between mineralization and survival could not be determined. We were unable to detect an association between any other nodule radiologic features and survival.ConclusionThe findings show that the presence of IPNs at diagnosis is associated with poorer survival of affected patients compared with those with normal staging chest CTs. IPNs noted at presentation in patients with high-grade osteosarcoma and spindle cell sarcoma of bone should be discussed with the patient and be considered when making treatment decisions. Further work is required to elucidate how the nodules should be managed.Level of EvidenceLevel III, prognostic study.     

Geriatric Trauma in a High-Volume Trauma Centre in Cape Town: How Do We Compare?

World Journal of Surgery - Little is known about the injury profile of older persons from low-and-middle-income countries, such as South Africa, where violence is prevalent. This study aimed to...     

How Should We Treat Patients with Locally Advanced Prostate Cancer?

Men with locally advanced prostate cancer are generally offered active treatment (radiotherapy or hormone therapy alone or in combination) with the aim of extending progression-free and overall survival. There is now good evidence from recent studies to suggest that patients who are treated with radiotherapy benefit from the addition of neoadjuvant or adjuvant hormone therapy. However, the extent of the contribution of radiotherapy in patients receiving hormone therapy is unclear, as the trials evaluating this combination approach did not include a hormone therapy only arm. Two ongoing trials, an International Intergroup study involving the National Cancer Institute of Canada (NCIC), the Medical Research Council (MRC), and the National Cancer Institute (NCI) in the United States, and a Scandinavian Prostate Cancer Group (SPCG) trial, are addressing this issue. Results should be available in the latter part of the decade. The optimum nature and schedule of hormone therapy are also unresolved. When hormone therapy is used to treat locally advanced disease, either as adjuvant therapy or immediate monotherapy, patients have traditionally undergone medical (e.g. goserelin [‘Zoladex’¹]) or surgical castration. However, bicalutamide (‘Casodex’¹) 150 mg monotherapy may offer important benefits over castration with respect to quality of life, particularly the maintenance of physical capacity and sexual interest, as well as preservation of bone mineral density and muscle mass, while achieving a similar survival outcome. Nonetheless, the benefits of bicalutamide 150 mg monotherapy must be balanced against the risk of developing gynecomastia and/or breast pain. Patients presenting with locally advanced prostate cancer should be given a clear explanation on all available treatment options and allowed to make an informed choice.     

Opportunity Lost? Diagnostic Laparoscopy in Patients with Pancreatic Cancer in the National Surgical Quality Improvement Program Database

World Journal of Surgery - Routine preoperative staging in pancreas cancer is controversial. We sought to evaluate the rates of diagnostic laparoscopy (DLAP) for pancreatic cancer. We queried the...