Does preoperative therapy optimize outcomes in patients with resectable pancreatic cancer?

The objective of this study was to compare survival between all patients with radiographically resectable adenocarcinoma of the proximal pancreas who underwent preoperative chemoradiation therapy (PRE‐OP CRT) or surgical exploration first (SURGERY) with “intention to resect.” Pancreatic cancer patients who undergo resection after PREOP CRT live longer than patients who undergo resection without PREOP CRT, a difference that may be attributable to patient selection. We retrospectively identified 236 patients with pancreatic head adenocarcinoma seen between 1999 and 2007 with sufficient data to be confirmed medically and radiographically resectable. The outcomes of 144 patients who underwent PREOP CRT were compared to those of 92 patients who proceeded straight to SURGERY. The groups were similar in age and gender. Tumors were slightly larger in the PREOP CRT group (mean 2.5 cm vs. 2.1 cm, P < 0.01), and there were trends toward more venous abutment (54% vs. 39%, P = 0.06) and a higher Charlson comorbidity index (P = 0.1). In the PREOP CRT group, 76 patients (53%) underwent resection, 28 (19%) had metastatic and 17 (12%) locally unresectable disease after PREOP CRT, and 23 (16%) were not explored due to performance status or loss to follow‐up. In the SURGERY group, 68 patients (74%) underwent resection. Sixteen patients (17%) had metastatic and eight patients (9%) locally unresectable disease at exploration. In patients who underwent resection, the PREOP CRT group had smaller pathologic tumor size and lower incidence of positive lymph nodes than the SURGERY group but no difference in positive margins or need for vascular resection. Median overall survival (OS) in patients undergoing resection was 27 months in the PREOP CRT group and 17 months in the SURGERY group (P = 0.04). Median OS in all patients treated with PREOP CRT or surgically explored with intention to resect was 15 and 13 months, respectively, with superimposable survival curves. Despite a lower resection rate, the PREOP CRT group as a whole had a similar OS to the SURGERY group as a whole. For patients who underwent resection, those in the PREOP CRT had longer survival than those in the SURGERY group, suggesting that PREOP CRT allows better patient selection for resection. PREOP CRT should be considered an acceptable alternative for most patients with resectable pancreatic cancer. J. Surg. Oncol. 2012; 106:111–118. © 2012 Wiley Periodicals, Inc.     

Does regional treatment improve the survival in patients with operable breast cancer?

Background. The impact of regional therapy on survival of patients with invasive breast cancer remains controversial. Regional therapies discussed include axillary lymph node dissection (ALND), internal mammary node dissection, and locoregional radiotherapy. Methods. Prospective randomized clinical studies of regional therapy were reviewed using, as a source, Medline, main review articles on the related topic, and statements from consensus conference. Results. Although a number of randomized clinical studies have failed to demonstrate the benefits of regional treatment for survival, it is still a matter of debate whether ALND or regional radiotherapy alone can have a small but significant beneficial effect on the survival of breast cancer patients. However, recent studies have suggested that survival can be enhanced by interaction of postmastectomy locoregional radiotherapy with adjuvant systemic therapy. Conclusions. Locoregional control is important for enhancing survival in the presence of adjuvant systemic therapy. Although only a few randomized controlled trials show conclusively the survival benefit of local therapies, it is expected that in clinical practice, the node-positive or other high-risk breast cancer patients given systemic treatment will be more frequently treated with postmastectomy radiation.     

Does age matter in the selection of treatment for men with early-stage prostate cancer?

BACKGROUND: The specific aim of the current study was to compare freedom from biochemical failure, distant metastases-free survival, and overall survival in men age < or = 55 years, men ages 60 to 69 years, and men age > or = 70 years presenting with localized prostate cancer. METHODS: A matched pair analysis compared patients age < or = 55 years (Group 1) who were treated with 3-dimension conformal radiation without androgen deprivation to men age > or = 60 years and < 70 years (Group 2), and men age > or = 70 years (Group 3) who were treated at the Fox Chase Cancer Center between November 1989 and October 2001. The groups were matched for disease stage (T1/T2b vs. T2C/T3), Gleason grade (2-6 vs. 7-10), radiation dose (< 70 Gray [Gy] vs. > or = 70-76 Gy vs. > or = 76 Gy), and pretreatment prostate-specific antigen (PSA) level. Estimates of outcome were accomplished using Kaplan-Meier methodology and compared by age group using the log-rank test. RESULTS: Eighty-four men were identified according to the selection criteria. No statistically significant difference was found in the 5-year overall survival rates for Group 1, Group 2, and Group 3 (94%, 95%, and 87%, respectively) or the 5-year rate of freedom from biochemical failure in Group 1, Group 2, and Group 3 (82%, 76%, and 70%, respectively), or freedom from distant metastases (96%, 97%, and 98%, respectively). CONCLUSIONS: Men age < or = 55 years who present with localized prostate cancer do not appear to have a worse prognosis. External beam radiation therapy appears to be a viable treatment alternative and should be offered to men age < or = 55 years who present with organ-confined prostate cancer.     

Does Gleason score at initial diagnosis predict efficacy of abiraterone acetate therapy in patients with metastatic castration-resistant prostate cancer? An analysis of abiraterone acetate phase III trials

BackgroundThe usefulness of Gleason score (<8 or ≥8) at initial diagnosis as a predictive marker of response to abiraterone acetate (AA) plus prednisone in patients with metastatic castration-resistant prostate cancer (mCRPC) was explored retrospectively.Patients and methodsInitial diagnosis Gleason score was obtained in 1048 of 1195 (COU-AA-301, post-docetaxel) and 996 of 1088 (COU-AA-302, chemotherapy-naïve) patients treated with AA 1 g plus prednisone 5 mg twice daily by mouth or placebo plus prednisone. Efficacy end points included radiographic progression-free survival (rPFS) and overall survival (OS). Distributions and medians were estimated by Kaplan–Meier method and hazard ratio (HR) and 95% confidence interval (CI) by Cox model.ResultsBaseline characteristics were similar across studies and treatment groups. Regardless of Gleason score, AA treatment significantly improved rPFS in post-docetaxel [Gleason score <8: median, 6.4 versus 5.5 months (HR = 0.70; 95% CI 0.56–0.86), P = 0.0009 and Gleason score ≥8: median, 5.6 versus 2.9 months (HR = 0.58; 95% CI 0.48–0.72), P < 0.0001] and chemotherapy-naïve patients [Gleason score <8: median, 16.5 versus 8.2 months (HR = 0.50; 95% CI 0.40–0.62), P < 0.0001 and Gleason score ≥8: median, 13.8 versus 8.2 months (HR = 0.61; 95% CI 0.49–0.76), P < 0.0001]. Clinical benefit of AA treatment was also observed for OS, prostate-specific antigen (PSA) response, objective response and time to PSA progression across studies and Gleason score subgroups.ConclusionOS and rPFS trends demonstrate AA treatment benefit in patients with pre- or post-chemotherapy mCRPC regardless of Gleason score at initial diagnosis. The initial diagnostic Gleason score in patients with mCRPC should not be considered in the decision to treat with AA, as tumour metastases may no longer reflect the histology at the time of diagnosis.Clinical trials numberCOU-AA-301 (NCT00638690); COU-AA-302 (NCT00887198).     

Does pain intensity predict a poor opioid response in cancer patients?

Aim

The aim of this study was to test the hypothesis that initial pain intensity is not a predictive factor of poor opioid response in advanced cancer patients, as suggested by a recent work.

Methods

A secondary analysis of one-hundred-sixty-seven patients referred for treatment of cancer-related pain was conducted. Pain intensity at admission was recorded and patients were divided in three categories of pain intensity: mild, moderate and severe. Patients were offered a treatment with opioid dose titration, according to department policy. Data regarding opioid doses and pain intensity were collected after dose titration was completed. Four levels of opioid response were considered: (a) good pain control, with minimal opioid escalation and without relevant adverse effects; (b) good pain control requiring more aggressive opioid escalation, for example doubling the doses in four days; (c) adequate pain control associated with the occurrence of adverse effects; (d) poor pain control with adverse effects.

Results

Seventy-six, forty-four, forty-one and six patients showed a response a, b, c, and d, respectively. No correlation between baseline pain intensity categories and opioid response was found. Patients with response ‘b’ and ‘d’ showed higher values of OEI mg.

Conclusion

Baseline pain intensity does not predict the outcome after an appropriate opioid titration. It is likely that non-homogeneous pain treatment would have biased the outcome of a previous work.     

Does long-term treatment with Doxil® predispose patients to oral cancer?

We present a possible adverse reaction related to long-term use of Doxil^® in female patients. We believe that long-term use of Doxil^® may predispose female patients to oral squamous cell carcinoma. The patients in this report were not exposed to the common risk factors related to oral cancer formation such as smoking or alcohol consumption. Both patients were 59-year-old females. The first patient was diagnosed in 2001 with stage IIIC ovarian cancer. Seven years following treatment with Doxil^®, she was diagnosed with stage III squamous cell carcinoma of the right maxilla. The second patient was diagnosed with Kaposi’s sarcoma with evidence of spread to the lungs. Four years following treatment with Doxil^® she was diagnosed with stage I squamous cell carcinoma of the left maxilla. A literature review did not reveal any report on Doxil^® and predisposition to oral cancer; however, we found an abstract that was presented at the last annual meeting of the American Society of Clinical Oncology (ASCO) by Cannon et al. When we combine the data from Cannon et al. and the data presented here, a total of six female patients developed an epithelial carcinoma of the oral cavity following long-term treatment with Doxil^®. We believe that a large-scale study should be initiated on patients that were treated with Doxil^® for more than 3 years, since these patients might be at risk for developing secondary cancer of the oral cavity.     

Is quadrant biopsy sufficient in men likely to have advanced prostate cancer? Comparison with extended biopsy

We hypothesized that quadrant prostate biopsy (QPB) provides sufficient first-line pathological evaluation of patients with presumed advanced prostate cancer (PC). The aim of this study was to investigate whether the reduction of core number in first-line PB from 6-12 to 4 in patients with presumed advanced PC leads to loss of clinically relevant information. We retrospectively studied 113 men that underwent PB, classified in two groups: "H" (high) and "L" (low likelihood of having advanced PC), according to PSA, digital rectal and transrectal ultrasound findings. Pathological results of 6-12-core PB and QPB were retrospectively compared for the presence of malignancy, percentage of positive cores, Gleason score (GS), and the presence of high-grade prostatic intraepithelial neoplasia (HGPIN). PC detection rate was not impaired in group H but dropped significantly in group L, and the percentage of positive cores was not significantly changed in group H (p=0.39), but decreased in group L (p=0.04), due to sampling scheme reduction. No HGPIN was missed with QPB in group H, while 2 HGPINs were missed in group L. No significant change in GS in either group was observed (p=0.12, p=0.13) due to reduction to QPB. We conclude that in patients with presumed advanced PC, reduction of the number of cores in PB may be an acceptable diagnostic strategy, but further studies are needed to analyze the impact of PB scheme reduction on other relevant pathological information obtained from PB.     

Does family history of prostate cancer affect outcomes following radiotherapy?

Objective

To examine family history (FH) as a prognostic factor following radiotherapy (RT).

Materials and methods

Between 1989 and 2007, 1711 men with clinically localized prostate cancer and complete family history who had received RT (median RT dose = 74 Gy) without androgen deprivation therapy were analyzed. FH was defined as any prostate cancer in a first degree relative. For the biochemical failure (BF) outcome, this sample size has 85% power to detect a hazard ratio of 1.56 for positive versus negative FH.

Results

With a median follow-up of 71 months, there was no significant difference in the distribution of Gleason score (GS) or prostate specific antigen (PSA) based on FH. A positive FH was not an independent predictor of BF, distant metastasis (DM), prostate cancer specific mortality (PCSM), or overall mortality (OM) in Cox proportional multivariable analysis. On further analysis in a Cox proportional multivariable analysis, men with two or more first degree relatives with prostate cancer had a significantly higher likelihood of BF and DM than those with no FH, although there was no difference in PCSM or OM. Men with a positive FH (23%) were more likely to be younger, have a lower PSA, and non-palpable disease. There was no interaction between a positive FH and neither race nor treatment era (pre-PSA vs. PSA era).

Conclusions

A positive FH is not a prognostic factor following RT and should not alter standard treatment recommendations. Patients with two or more first degree relatives with prostate cancer had a higher likelihood of BF and DM, but there was no effect on survival. There was no interaction between a positive FH and African American race or treatment era. A positive FH was however, associated with more favorable PSA values and T-stage that may be the result of earlier screening.     

Should we follow-up serum testosterone in patients with advanced prostate cancer?

Agonistic analogs of luteinizing hormone-releasing hormones are indicated for the palliative treatment of metastatic prostate cancer. While the prognostic role of prostate-specific antigen in patients submitted to androgen-deprivation therapy has been extensively investigated in these patients, there is no consensus about the utility of serum testosterone measurements during follow-up and about their possible prognostic value. Recent reports have shown that testosterone levels might be directly related to survival and risk of death. These results need to be confirmed by further prospective studies. Given this concept, lowering testosterone as much as possible should be the goal of androgen-deprivation therapy in patients with metastatic prostate cancer, as this may have an impact on patient survival.     

Phase II study of vinorelbine in patients with androgen-independent prostate?cancer

Purpose:To evaluate the efficacy and toxicity ofvinorelbine in a phase II study in patients with progressive metastaticandrogen-independent prostate cancer. Patients and methods:Forty-seven men with progressivemetastatic prostate cancer refractory to first-line or second-linehormonal therapy were treated with vinorelbine, a semi-syntheticvinca-alkaloid. Vinorelbine was given, on an outpatient schedule, at 25mg/m² weekly for at least eight weeks or until progression orexcessive toxicity. Results: Forty-seven patients were included in the study, 33being evaluable for tumour response, 36 for response to PSA, 21 forclinical benefit and 45 for toxicity. Median actual weekly dose was 19mg/m² (range 12.0–26.2 mg/m²). Six ofthirty-six patients (17%) demonstrated a biologic response with a50% or more decline in serum PSA on two consecutivemeasurements taken at least two weeks apart. The median durationof biologic response was 2.7 months. Two of three patientswith measurable disease obtained an objective response but remainedunconfirmed. No change disease was reported in 23 patients (49%).On entry into the study, 30 patients had symptomatic bone pain andrequired narcotic or non-narcotic analgesics. Clinical benefit fromvinorelbine was achieved in 15 patients out of 21 (32% of theintent to treat analysis population and 71% of the assessablepatients). Due to the low number of questionnaires (QLQ-C30) filled in,it was insufficient to allow any statistical analysis. The mediansurvival was 10.2 months. Toxicity was mainly haematologic with51% of patients experiencing grade 3 or 4 granulocytopenia. Threepatients developed deep vein thrombosis. Non-haematologic toxicity,mainly nausea and neurotoxicity, was mild. Conclusion:The administration of weekly vinorelbine appearsto be a safe treatment for those patients with androgen-independentprostate cancer and poor prognosis features who require chemotherapy.These results provide data for future investigation of vinorelbine incombination regimens.     

Clinical tools to predict outcomes in patients with esophageal cancer treated with definitive chemoradiation: are we there yet?

Definitive chemoradiation (CRT) is a well-established treatment for esophageal cancer, but disease recurrence is common and many patients do not achieve initial remission with CRT alone. Predictors of outcome with CRT are needed to guide prognosis and further treatment decisions, in particular the need for post-CRT surgery. We review the role of baseline clinical factors, such as histology and tumor bulk, in predicting response to CRT. Post-CRT assessments, particularly PET imaging, may provide further information about the likelihood of complete response and survival, but the predictive power of clinical assessments remains limited. Emerging research on biomarkers holds promise for more tailored and accurate prediction of outcome with definitive CRT.