Purpose
Surveillance after colorectal cancer (CRC) treatment is routine, but intensive follow-up may offer little-to-no overall survival benefit. Given the growing population of CRC survivors, we aimed to systematically evaluate the literature for the patient perspective on 2 questions: (1) How do CRC patients perceive routine surveillance following curative treatment and what do they expect to gain from their surveillance testing or visits? (2) Which providers (specialists, nursing, primary care) are preferred by CRC survivors to guide post-treatment surveillance?
Methods
Systematic searches of PubMed MEDLINE, Embase, the CENTRAL Register of Controlled Trials, CINAHL and PsycINFO were conducted. Studies were screened for inclusion by 2 reviewers, with discrepancies adjudicated by a third reviewer. Data were abstracted and evaluated utilizing validated reporting tools (CONSORT, STROBE, CASP) appropriate to study design.
Results
3691 citations were screened, 91 full-text articles reviewed, and 23 studies included in the final review, 15 quantitative and 8 qualitative. Overall, 12 studies indicated CRC patients perceive routine surveillance positively, expecting to gain reassurance of continued disease suppression. Negative perceptions described in 6 studies included anxiety and dissatisfaction related to quality of life or psychosocial issues during follow-up. Although 5 studies supported specialist-led care, 9 studies indicated patient willingness to have follow-up with non-specialist providers (primary care or nursing).
Conclusions
Patients’ perceptions of follow-up after CRC are predominantly positive, although unmet needs included psychosocial support and quality of life.
Implications for Cancer Survivors
Survivors perceived follow-up as reassuring, however, surveillance care should be more informative and focused on survivor-specific needs.
dMMR biliary tract cancers associated with LS are rare but long-term outcomes may be more favorable than contemporaneous cohorts of non-Lynch-associated cholangiocarcinomas. Given the emerging promise of immunotherapy for patients with dMMR malignancies, tumor testing for dMMR followed by confirmatory germline testing should be considered in patients with BTC and a personal history of other LS cancers.
Purpose
Determination of microsatellite instability (MSI) by PCR is the gold standard; however, immunohistochemistry (IHC) of mismatch repair (MMR) proteins is frequently performed instead. The reliability of these methods on post-neoadjuvant-therapy specimens is unknown. We examined the effect of neoadjuvant therapy on MSI results by PCR and IHC.
Experimental design
A total of 239 colorectal cancers resected after neoadjuvant therapy were assessed for MSI with PCR and IHC. PCR and IHC results for matched paired pre- and post-treatment specimens were compared. In parallel, two isogenic cell lines conditioned for MMR functioning and two different patient-derived xenografts (PDX) were exposed to chemotherapy, radiation or both. We also examined whether establishment of PDXs induced MSI changes in five tumors. IHC and MSI were tested after treatment to assess for changes.
Results
We identified paired pre- and post-treatment specimens for 37 patients: 2 with PCR only, 34 with IHC only, and 1 with both. All three patients with PCR had microsatellite stable pre- and post-treatment specimens. Of the 35 patients with IHC, 30 had intact MMR proteins in pre- and post-treatment specimens, 1 had equivocal MLH1 staining in the pre-treatment and loss in the post-treatment specimen, and 4 had intact pre-treatment MSH6 but variable post-treatment staining. In the experimental setting, no changes in MSI status were detected after treatment or tumor implantation in animals.
Conclusions
Our findings show that expression of MMR proteins, commonly MSH6, can change after neoadjuvant therapy and confirm PCR as the gold-standard test for MSI after neoadjuvant therapy.
tions were twice as likely in patients undergoing a repeated breast surgery (16.2%; 95% CI, 14.7%-17.7% vs 7.9%; 95% CI, 7.3%-8.5%; P < .001). Increased complications owing to a repeated surgery were statistically significant.Discussion | These data demonstrate that in 23.2% of BCS patients, the full benefits of BCS are not realized owing to the added costs and complications of subsequent surgery. For example, mastectomy is associated with a 15.7% 2-year infection rate, 4 which is similar to the 15.3% experienced by repeated-surgery patients. Patients undergoing additional surgeries incur an average $16 072 in added health care costs. Indeed, reexcision after BCS owing to margin status has been deemed "the other breast cancer epidemic." 5 Notably, the data in this work preceded the recent SSO-ASTRO margin guidelines, which may impact future repeated surgery rates. Although many women will continue to benefit from BCS, these findings demonstrate quantitative evidence of a patientcentered and fiscal requirement to implement techniques to reduce BCS reoperations, including advanced margin evaluation. 6
Lynch syndrome is the most common Mendelian disorder predisposing to hereditary colorectal cancer. Carriers of MSH6 mutations constitute less than 10% of total cases and present with a weaker clinical phenotype, including low levels of microsatellite instability (MSI-L) in colorectal tumors. The frequency of MSH6 mutation carriers among patients presenting with MSI-L colorectal cancer has yet to be determined, as has the appropriate genetic work-up in this context. We have reviewed here the clinicopathological characteristics, immunohistochemistry and genetic testing results for 71 patients at a single institution diagnosed with MSI-L colorectal cancers. Of 71 patients with MSI-L tumors, 21 underwent genetic testing for MSH6 mutations, three of them presented with loss of staining of MSH6 and only one carried a pathogenic germline MSH6 mutation in exon 4 (c.2677_2678delCT; p.Leu893Alafs*6). This latter patient had a significant family history and had a rectal primary that showed instability only in mononucleotide markers. In this cohort of MSI-L patients, we detected no notable clinicopathological and molecular characteristics that would help to distinguish a group most likely to harbor germline MSH6 mutations. Therefore, we conclude that the prevalence of MSH6 mutations among subjects with MSI-L tumors is very low. MSI analysis combined with immunohistochemistry of mismatch repair proteins adequately detects potential MSH6 carriers among MSI-L colorectal cancers.
Lynch syndrome (LS) is a genetic condition secondary to germline alterations in the DNA mismatch repair (MMR) genes with 30% of changes being variants of uncertain significance (VUS). Our aim was to perform an in silico re-classification of VUS from a large single institutional cohort that will help prioritizing functional validation. A total of 54 VUS were detected with 33 (61%) novel variants. We integrated family history, pathology, and genetic information along with supporting evidence from 8 different in silico tools at the RNA and protein level. Our assessment allowed us to re-classify 54% (29/54) of the VUS as probably damaging, 13% (7/54) as possibly damaging and 28% (15/54) as probably neutral. There are more than 1,000 VUS reported in MMR genes and our approach facilitates the prioritization of further functional efforts to assess the pathogenicity to those classified as probably damaging.
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