The risk of death from index- and nonindex-cancers varies widely among primary sites. Risk of noncancer deaths now surpasses that of cancer deaths, particularly for young patients in the year after diagnosis.

BackgroundPain due to bone metastases is a common cause of cancer-related morbidity, with few options available for patients refractory to medical therapies and who do not respond to radiation therapy. This study assessed the safety and efficacy of magnetic resonance-guided focused ultrasound surgery (MRgFUS), a noninvasive method of thermal tissue ablation for palliation of pain due to bone metastases.MethodsPatients with painful bone metastases were randomly assigned 3:1 to receive MRgFUS sonication or placebo. The primary endpoint was improvement in self-reported pain score without increase of pain medication 3 months after treatment and was analyzed by Fisher’s exact test. Components of the response composite, Numerical Rating Scale for pain (NRS) and morphine equivalent daily dose intake, were analyzed by t test and Wilcoxon rank-sum test, respectively. Brief Pain Inventory (BPI-QoL), a measure of functional interference of pain on quality of life, was compared between MRgFUS and placebo by t test. Statistical tests were two-sided.ResultsOne hundred forty-seven subjects were enrolled, with 112 and 35 randomly assigned to MRgFUS and placebo treatments, respectively. Response rate for the primary endpoint was 64.3% in the MRgFUS arm and 20.0% in the placebo arm (P < .001). MRgFUS was also superior to placebo at 3 months on the secondary endpoints assessing worst score NRS (P < .001) and the BPI-QoL (P < .001). The most common treatment-related adverse event (AE) was sonication pain, which occurred in 32.1% of MRgFUS patients. Two patients had pathological fractures, one patient had third-degree skin burn, and one patient suffered from neuropathy. Overall 60.3% of all AEs resolved on the treatment day.ConclusionsThis multicenter phase III trial demonstrated that MRgFUS is a safe and effective, noninvasive treatment for alleviating pain resulting from bone metastases in patients that have failed standard treatments.

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Colorectal cancer (CRC) is increasingly appreciated as a heterogeneous disease, with factors such as microsatellite instability (MSI), cancer subsite within the colon versus rectum, and age of diagnosis associated with specific disease course and therapeutic response. Activating oncogenic mutations in KRAS and NRAS are common in CRC, driving tumor progression and influencing efficacy of both cytotoxic and targeted therapies. The RAS mutational spectrum differs substantially between tumors arising from distinct tissues. Structure-function analysis of relatively common somatic RAS mutations in G12, Q61, and other codons is characterized by differing potency and modes of action. Here we show the mutational profile of KRAS , NRAS , and the less common HRAS in 13,336 CRC tumors, comparing the frequency of specific mutations based on age of diagnosis, MSI status, and colon versus rectum subsite. We identify mutation hotspots, and unexpected differences in mutation spectrum, based on these clinical parameters.

Purpose: The incidence rates of colorectal cancers are increasing in young adults. The objective of this study was to investigate genomic differences between tumor samples collected from younger and older patients with colorectal cancer.Experimental Design: DNA was extracted from 18,218 clinical specimens, followed by hybridization capture of 3,769 exons from 403 cancer-related genes and 47 introns of 19 genes commonly rearranged in cancer. Genomic alterations (GA) were determined, and association with patient age and microsatellite stable/microsatellite instability high (MSS/MSI-H) status established.Results: Overall genomic alteration rates in the younger (<40) and older (!50) cohorts were similar in the majority of the genes analyzed. Gene alteration rates in the microsatellite stable (MSS) younger and older cohorts were largely similar, with several notable differences. In particular, TP53(FDR < 0.01) and CTNNB1 (FDR ¼ 0.01) alterations were more common in younger patients with colorectal cancer, and APC (FDR < 0.01), KRAS (FDR < 0.01), BRAF (FDR < 0.01), and FAM123B (FDR < 0.01) were more commonly altered in older patients with colorectal cancer. In the MSI-H cohort, the majority of genes showed similar rate of alterations in all age groups, but with significant differences seen in APC (FDR < 0.01), BRAF (FDR < 0.01), and KRAS (FDR < 0.01).Conclusions: Tumors from younger and older patients with colorectal cancer demonstrated similar overall rates of genomic alteration. However, differences were noted in several genes relevant to biology and response to therapy. Further study will need to be conducted to determine whether the differences in gene alteration rates can be leveraged to provide personalized therapies for young patients with early-onset sporadic colorectal cancer. Figure 5. Differing rates of specific BRAF and RNF43 mutations by age showing a clear distinction between BRAF V600E mutations versus other BRAF mutations as well as a difference in RNF43 659_660 mutations and RNF43 117 mutations.Genomic Landscape Young-Onset CRC www.aacrjournals.org

BACKGROUND The incidence of rectal cancer in the United States in young patients is considered to be low. Under-estimating this incidence may result in a failure to diagnose younger patients with rectal cancer in a timely manner. METHODS The authors conducted a retrospective cohort study using Surveillance, Epidemiology, and End Results (SEER) cancer registry data. A total of 7661 patients with colon, rectal, and rectosigmoid cancer who were diagnosed at age <40 years were identified between 1973 and 2005. The change in incidence over time for colon and rectal/rectosigmoid cancer was calculated and the annual percent change for anatomic subsites of colorectal cancer compared. RESULTS SEER data demonstrated an increase in the incidence of rectal cancer without any increase in colon cancer (annual percent change of 2.6% vs −0.2%). The difference was statistically significant and extended to rectosigmoid cancer, but not cancer of the sigmoid colon or descending colon (annual percent change of 2.2% vs 0.4% and −2.8%, respectively). Joinpoint analysis of the slope of the curve of rectal and rectosigmoid cancer incidence identified the beginning of the increase to be 1984. All races and both sexes demonstrated similar statistically significant increases in the incidence of rectal and rectosigmoid cancer. CONCLUSIONS The incidence of rectal and rectosigmoid cancer appears to be increasing in patients aged <40 years. Patients presenting with rectal bleeding or other alarming signs or symptoms should be evaluated with this finding in mind.

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Background The interval between neoadjuvant chemoradiation treatment and surgery has been described as an important predictor of pathologic response to therapy in non-esophageal cancer sites. We retrospectively reviewed our experience with patients who underwent neoadjuvant chemoradiation and esophagectomy to better understand the impact of the timing of surgery on pathologic complete response rates in esophageal cancer. Methods Two hundred thirty one sequentially treated patients from 2000 to 2011 were identified for this study, 88 of these patients completed neoadjuvant chemoradiation followed by esophagectomy at our institution. The interval between completion of chemoradiation and surgery was calculated for each patient. The patients were categorized into quartiles and also 3-week interval groups. Treatment factors and surgical morbidity data including the estimated blood loss and length of operative stay were also assessed. Results Quartiles for the neoadjuvant chemoradiation to surgery interval were <45 days, 46-50 days, 51-63 days, and 64+ days. Corresponding pathologic complete response rates were 12.5%, 20.0%, 22.7% and 40.9% (p=0.03). Results for 3-week intervals were similar (p=0.02). There was no association between increasing time interval between the ending of neoadjuvant chemoradiation to surgery and length of stay longer than 2 weeks. Conclusions A longer interval between completion of neoadjuvant chemoradiation and surgery was associated with higher pathologic complete response rates without an impact on surgical morbidity.