Palliative prognostic Score in terminally ill cancer patients.

An existing and validated palliative prognostic (PaP) score predicts survival in terminally ill cancer patients based on dyspnea, anorexia, Karnofsky performance status score, clinical prediction of survival, total WBC, and lymphocyte percentage. The PaP score assigns patients to three different risk groups according to a 30-day survival probability—group A, >70%; group B, 30%–70%; group C, <30%. The impact of delirium is known but was not incorporated into the PaP score.

Materials and Methods. Our aim was to incorporate information on delirium into the PaP score based on a retrospective series of 361 terminally ill cancer patients. We followed the approach of “validation by calibration,” proposed by van Houwelingen and later adapted by Miceli for achieving score revision with inclusion of a new variable. The discriminating performance of the scores was estimated using the K statistic.

Results. The prognostic contribution of delirium was confirmed as statistically significant (p < .001) and the variable was accordingly incorporated into the PaP score (D-PaP score). Following this revision, 30-day survival estimates in groups A, B, and C were 83%, 50%, and 9% for the D-PaP score and 87%, 51%, and 16% for the PaP score, respectively. The overall performance of the D-PaP score was better than that of the PaP score.

Conclusion. The revision of the PaP score was carried out by modifying the cutoff values used for prognostic grouping without, however, affecting the partial scores of the original tool. The performance of the D-PaP score was better than that of the PaP score and its key feature of simplicity was maintained.

Source:The Oncologist.

The Effect of Cigarette Smoking on Cancer Treatment–Related Side Effects.

Cigarette smoking has long been implicated in cancer development and survival. However, few studies have investigated the impact of smoking on symptom burden in cancer survivors during treatment and at survivorship stage. This study examines the influence of cigarette smoking on side effects among 947 cancer patients during and 6 months following treatment.

Methods. Patients diagnosed with cancer and scheduled to receive chemotherapy and/or radiation therapy reported on current smoking status (yes, no) and total symptom burden [the sum of 12 common symptoms (fatigue, hair loss, memory, nausea, depression, sleep, pain, concentration, hot flashes, weight loss, skin problems, and dyspnea) scored on an 11-point scale ranging from 0 = “not present” to 10 = “as bad as you can imagine”] during treatment and at 6-month follow-up. The adjusted mean total symptom burden by smoking status was determined by analysis of covariance controlling for age, gender, race, education, occupation, treatment, cancer site, and Karnofsky performance score.

Results. During treatment, smokers (S) had a significantly higher total symptom burden than nonsmokers (NS) (S = 46.3 vs. NS = 41.2; p < 0.05). At 6-month follow-up, smokers continued to report a higher total symptom burden than nonsmokers (S = 27.7 vs. NS = 21.9; p < 0.05). Participants who quit smoking before treatment levels had a total symptom burden similar to nonsmokers.

Conclusion. Smoking was associated with an increased symptom burden during and following treatments for cancer. Targeted cessation efforts for smokers to decrease symptom burden may limit the likelihood of treatment interruptions and increase quality of life following treatment.

Source:The Oncologist.


When to Wait for More Evidence? Real Options Analysis in Proton Therapy.

Trends suggest that cancer spending growth will accelerate. One method for controlling costs is to examine whether the benefits of new technologies are worth the extra costs. However, especially new and emerging technologies are often more costly, while limited clinical evidence of superiority is available. In that situation it is often unclear whether to adopt the new technology now, with the risk of investing in a suboptimal therapy, or to wait for more evidence, with the risk of withholding patients their optimal treatment. This trade-off is especially difficult when it is costly to reverse the decision to adopt a technology, as is the case for proton therapy. Real options analysis, a technique originating from financial economics, assists in making this trade-off.

Methods. We examined whether to adopt proton therapy, as compared to stereotactic body radiotherapy, in the treatment of inoperable stage I non-small cell lung cancer. Three options are available: adopt without further research; adopt and undertake a trial; or delay adoption and undertake a trial. The decision depends on the expected net gain of each option, calculated by subtracting its total costs from its expected benefits.

Results. In The Netherlands, adopt and trial was found to be the preferred option, with an optimal sample size of 200 patients. Increase of treatment costs abroad and costs of reversal altered the preferred option.

Conclusion. We have shown that real options analysis provides a transparent method of weighing the costs and benefits of adopting and/or further researching new and expensive technologies.

Source:The Oncologist.



Age-Specific Administration of Chemotherapy and Long-Term Quality of Life in Stage II and III Colorectal Cancer Patients: A Population-Based Prospective Cohort.

Purpose. To investigate the age-specific pattern of administration of chemotherapy and its association with long-term survival and quality of life (QoL) in stage II and III colorectal cancer patients.

Methods. Chemotherapy allocation according to disease and patient characteristics was investigated in a population-based cohort of 562 stage II and III colorectal cancer patients. Five years after diagnosis, survival was determined and QoL was assessed using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 Items and a tumor specific module. The association among chemotherapy, survival, and QoL was examined while controlling for potential confounders.

Results. Chemotherapy was administered in 71% of patients aged <60 years and in only 20% of patients aged ≥80 years. A significant association between chemotherapy and longer survival time was found for stage III cancer only. Chemotherapy was associated with higher symptom levels for trouble with taste, anxiety, and hair loss. In age-specific analyses, younger survivors (<70 years at time of follow-up) with a history of chemotherapy reported significantly lower physical, role, and cognitive functioning and higher pain, appetite loss, hair loss, and trouble with taste symptom levels. In contrast, for older survivors (≥70 years), only two (hair loss and dry mouth) out of 38 QoL scores were significantly associated with chemotherapy.

Discussion. Chemotherapy is associated with lower long-term QoL, especially in younger survivors. In cases of uncertain survival benefits of chemotherapy, consideration of its long-term effects on QoL should be incorporated into final decisions on treatment.

Source:The Oncologist.


Toxicity as a Biomarker of Efficacy of Molecular Targeted Therapies: Focus on EGFR and VEGF Inhibiting Anticancer Drugs.

In addition to being present in tumor cells, many targets of signal transduction inhibitors are also found in normal tissue. Side effects attributable to the mechanism of action of molecular targeted agents thus represent “on-target” modulation in normal tissues. These mechanism-based toxicities can be pharmacodynamic effects of pathway inhibition and, in tumors depending on the inhibited pathway for proliferation, might be biomarkers of efficacy. The development of rash with tyrosine kinase inhibitors or monoclonal antibodies targeting the epidermal growth factor receptor is associated with superior outcomes in lung, head and neck, colorectal, and pancreatic cancer studies. Correlated with superior efficacy in retrospective analyses of large studies in advanced colorectal, breast, and renal cell carcinoma, arterial hypertension as an adverse event of antiangiogenic agents may also be a marker of effective target inhibition. An association between hypothyroidism and the activity of multitargeted tyrosine kinase inhibitors has been identified in renal cell carcinoma patients. Tumor growth addiction to the specific pathway that is effectively targeted may be the link between a mechanism-based toxicity and efficacy. The biological basis for this correlation can be pharmacological, with higher drug exposure being associated with greater toxicity and antitumor activity, and can also be genetic, because single nucleotide polymorphisms play an important role in drug pharmacokinetic and pharmacodynamic processes. Investigators have proposed that interpatient differences and associated toxicities can be exploited for dose selection and titration, and clinical trials are currently exploring intrapatient “dosing-to-toxicity” strategies. Ultimately, the predictive value of a side effect of molecular targeted therapies requires validation in prospective trials.

Source:The Oncologist.

The Outcomes and Safety of Single-Agent Sorafenib in the Treatment of Elderly Patients with Advanced Hepatocellular Carcinoma (HCC)

With the aging population, hepatocellular carcinoma (HCC) in the elderly represents a significant health burden. We aimed to evaluate and compare the efficacy and tolerability of single-agent sorafenib in treating elderly patients with advanced HCC versus the younger population.

Methods. We retrospectively analyzed a consecutive cohort of advanced HCC patients with Child-Pugh A or B liver function and an Eastern Cooperative Oncology Group performance status score of 0–2 treated with sorafenib. The patients were categorized into older (age ≥70 years) and younger (age <70 years) groups. Treatment outcomes and related adverse events (AEs) were compared.

Results. In total, 172 patients, 35 in the older (median age, 73 years) and 137 in the younger (median age, 55 years) group, were analyzed. The median progression-free survival time was similar in the older and younger groups (2.99 months versus 3.09 months; p = .275), as was the overall survival time (5.32 months versus 5.16 months; p = .310). Grade 3 or 4 AEs were observed in 68.6% of older and 62.7% of younger patients (p = .560), with neutropenia (11.4% versus 0.7%; p = .007), malaise (11.4% versus 2.2%; p = .033), and mucositis (5.7% versus 0.0%; p = .041) being more frequently reported in the elderly cohort.

Conclusions. The survival benefits and overall treatment-related AEs of sorafenib are comparable in elderly and younger advanced HCC patients. Nevertheless, more vigilant monitoring in the elderly is warranted because they are more susceptible to develop neutropenia, malaise, and mucositis.

Source:The Oncologist.



Acinar Cell Carcinoma of the Pancreas: New Genetic and Treatment Insights into a Rare Malignancy.

Acinar cell carcinoma (ACC) of the pancreas is a rare neoplasm, accounting for 1% of all pancreatic neoplasms. There remains a lack of data regarding the use of systemic therapy in this disease. We present a series of 40 consecutive cases of ACC of the pancreas treated at Memorial Sloan-Kettering Cancer Center, with an emphasis on evaluation of activity of new therapeutic agents.

Methods. Patients reviewed at our institution from January 2000 through January 2011 were identified from an institutional database with prior institutional review board approval. Pathology was confirmed in all cases as ACC or a closely related entity.

Results. Forty patients were identified; 29 were male (73%). The median age at diagnosis was 65 years (range, 16–87 years). The median overall survival (OS) time for patients with localized, resectable disease was 56.9 months and the OS time for patients with metastatic ACC (n = 18) was 19.6 months. Six patients with metastatic or recurrent ACC had a partial response to chemotherapy and five patients had stable disease for ≥6 months on systemic chemotherapy. Clinical observation was made of a patient with ACC and hereditary nonpolyposis colorectal cancer and a patient with ACC and a BRCA1 germline mutation.

Conclusions. ACC is moderately chemoresponsive to agents that have activity in pancreatic adenocarcinoma and colorectal carcinoma. A potential association between germline mutations in DNA mismatch repair genes and ACC warrants further evaluation.

Source:The Oncologist.



Overexpression/Amplification on the Prognosis of Gastric Cancer Patients Undergoing Resection: A Single-Center Study of 1,036 Patients.

Opinions regarding the impact of human epidermal growth factor receptor (HER)-2 overexpression or HER-2amplification on the prognosis of gastric cancer patients are mixed. The present study attempted to clarify this issue by investigating a large cohort of surgical patients.

Methods. We investigated 1,036 gastric cancer patients undergoing curative-intent resection. Their surgical specimens were evaluated for HER-2 expression by immunohistochemistry (IHC), and those with HER-2 expression levels of 2+ were additionally subjected to fluorescence in situ hybridization (FISH). Data on demographic and clinicopathological features and relevant prognostic factors in these patients were analyzed.

Results. HER-2 positivity was noted in 64 (6.1%) of 1,036 gastric cancer patients, including 46 patients whose HER-2 expression level was 3+ on IHC and 18 patients whose FISH results were positive. On univariate analysis, HER-2 positivity was more often associated with differentiated histology, intestinal type, and negative resection margins, whereas only differentiated histology was independently associated with HER-2 positivity in a logistic regression model. For stage I–IV gastric cancer, HER-2 was not a prognostic factor. In a subpopulation study, although HER-2 positivity emerged as a favorable prognostic factor for stage III–IV gastric cancer on univariate analysis, it failed to be an independent prognostic factor after multivariate adjustment.

Conclusions. The prevalence of HER-2 positivity, determined using standardized assays and scoring criteria in a large cohort of gastric cancer patients after resection, was 6.1%. HER-2 positivity was phenotypically associated with differentiated histology. HER-2 is not an independent prognostic factor for gastric cancer.

Source:The Oncologist.

Prevalence of Skin Lesions in Familial Adenomatous Polyposis: A Marker for Presymptomatic Diagnosis?

Benign skin tumors such as lipomas, fibromas, and epidermal cysts are among the extracolonic manifestations of familial adenomatous polyposis (FAP). Readily detectable by inspection, they could serve as presymptomatic diagnostic markers to identify FAP patients. We therefore prospectively determined the prevalence of cutaneous lesions in genetically confirmed adenomatous polyposis coli (APC) mutation carriers and assessed their potential usefulness in the identification of FAP patients.

Methods. Whole-skin examination was performed in 56 adult APC mutation carriers, compared with a control group (n = 116). In addition, FAP patients were investigated for the presence of congenital hypertrophy of the retinal pigment epithelium (CHRPE), an established clinical marker for FAP, and a detailed review of medical records was performed.

Results. Nearly half of all FAP patients (48.2%) had at least one FAP-associated skin lesion, compared with one third (34.5%) of controls. Only multiple lipomas and combined skin lesions were significantly more prevalent in APC mutation carriers. CHRPE was observed in 22 (43.1%) of 51 FAP patients, including 14 (37.8%) of 37 individuals with APC mutations outside the CHRPE-associated region between codons 311 and 1465.

Conclusions. Despite a significantly higher prevalence of multiple lipomas, occurring at younger age, and combined skin lesions in APC mutation carriers, the low diagnostic sensitivity of FAP-associated skin lesions precludes their use as markers for FAP in clinical practice. Based on our findings, the common CHRPE-associated region should be extended to APC codons 148-2043.

Source:The Oncologist.