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2. Characteristics of Early-Onset vs Late-Onset Colorectal Cancer A Review

Author

Zaborowski, AM, Abdile, A, Adamina, M, Aigner, F, d'Allens, L, Allmer, C, Alvarez, A, Anula, R, Andric, M, Atallah, S, Bach, S, Bala, M, Barussaud, M, Bausys, A, Bebington, B, Beggs, A, Bellolio, F, Bennett, M-R, Berdinskikh, A, Bevan, V, Biondo, S, Bislenghi, G, Bludau, M, Boutall, A, Brouwer, N, Brown, C, Bruns, C, Buchanan, DD, Buchwald, P, Burger, JWA, Burlov, N, Campanelli, M, Capdepont, M, Carvello, M, Chew, H-H, Christoforidis, D, Clark, D, Climent, M, Cologne, KG, Contreras, T, Croner, R, Daniels, IR, Dapri, G, Davies, J, Delrio, P, Denost, Q, Deutsch, M, Dias, A, D'Hoore, A, Drozdov, E, Duek, D, Dunlop, M, Dziki, A, Edmundson, A, Efetov, S, El-Hussuna, A, Elliot, B, Emile, S, Espin, E, Evans, M, Faes, S, Faiz, O, Fleming, F, Foppa, C, Fowler, G, Frasson, M, Figueiredo, N, Forgan, T, Frizelle, F, Gadaev, S, Gellona, J, Glyn, T, Gong, J, Goran, B, Greenwood, E, Guren, MG, Guillon, S, Gutlic, I, Hahnloser, D, Hampel, H, Hanly, A, Hasegawa, H, Iversen, LH, Hill, A, Hill, J, Hoch, J, Hoffmeister, M, Hompes, R, Hurtado, L, Iaquinandi, F, Imbrasaite, U, Islam, R, Jafari, MD, Kanemitsu, Y, Karachun, A, Karimuddin, AA, Keller, DS, Kelly, J, Kennelly, R, Khrykov, G, Kocian, P, Koh, C, Kok, N, Knight, KA, Knol, J, Kontovounisios, C, Korner, H, Krivokapic, Z, Kronberger, I, Kroon, HM, Kryzauskas, M, Kural, S, Kusters, M, Lakkis, Z, Lankov, T, Larson, D, Lazar, G, Lee, K-Y, Lee, SH, Lefevre, JH, Lepisto, A, Lieu, C, Loi, L, Lynch, C, Maillou-Martinaud, H, Maroli, A, Martin, S, Martling, A, Matzel, KE, Mayol, J, McDermott, F, Meurette, G, Millan, M, Mitteregger, M, Moiseenko, A, Monson, JRT, Morarasu, S, Moritani, K, Moslein, G, Munini, M, Nahas, C, Nahas, S, Negoi, I, Novikova, A, Ocares, M, Okabayashi, K, Olkina, A, Onate-Ocana, L, Otero, J, Ozen, C, Pace, U, Juliao, GPS, Panaiotti, L, Panis, Y, Papamichael, D, Park, J, Patel, S, Uriburu, JCP, Pera, M, Perez, RO, Petrov, A, Pfeffer, F, Phang, PT, Poskus, T, Pringle, H, Proud, D, Raguz, I, Rama, N, Rasheed, S, Raval, MJ, Rega, D, Reissfelder, C, Meneses, JCR, Ris, F, Riss, S, Rodriguez-Zentner, H, Roxburgh, CS, Saklani, A, Salido, AJ, Sammour, T, Saraste, D, Schneider, M, Seishima, R, Sekulic, A, Seppala, T, Sheahan, K, Shine, R, Shlomina, A, Sica, GS, Singnomklao, T, Siragusa, L, Smart, N, Solis, A, Spinelli, A, Staiger, RD, Stamos, MJ, Steele, S, Sunderland, M, Tan, K-K, Tanis, PJ, Tekkis, P, Teklay, B, Tengku, S, Jimenez-Toscano, M, Tsarkov, P, Turina, M, Ulrich, A, Vailati, BB, van Harten, M, Verhoef, C, Warrier, S, Wexner, S, de Wilt, H, Weinberg, BA, Wells, C, Wolthuis, A, Xynos, E, You, N, Zakharenko, A, Zeballos, J, Winter, DC, Zaborowski, AM, Abdile, A, Adamina, M, Aigner, F, d'Allens, L, Allmer, C, Alvarez, A, Anula, R, Andric, M, Atallah, S, Bach, S, Bala, M, Barussaud, M, Bausys, A, Bebington, B, Beggs, A, Bellolio, F, Bennett, M-R, Berdinskikh, A, Bevan, V, Biondo, S, Bislenghi, G, Bludau, M, Boutall, A, Brouwer, N, Brown, C, Bruns, C, Buchanan, DD, Buchwald, P, Burger, JWA, Burlov, N, Campanelli, M, Capdepont, M, Carvello, M, Chew, H-H, Christoforidis, D, Clark, D, Climent, M, Cologne, KG, Contreras, T, Croner, R, Daniels, IR, Dapri, G, Davies, J, Delrio, P, Denost, Q, Deutsch, M, Dias, A, D'Hoore, A, Drozdov, E, Duek, D, Dunlop, M, Dziki, A, Edmundson, A, Efetov, S, El-Hussuna, A, Elliot, B, Emile, S, Espin, E, Evans, M, Faes, S, Faiz, O, Fleming, F, Foppa, C, Fowler, G, Frasson, M, Figueiredo, N, Forgan, T, Frizelle, F, Gadaev, S, Gellona, J, Glyn, T, Gong, J, Goran, B, Greenwood, E, Guren, MG, Guillon, S, Gutlic, I, Hahnloser, D, Hampel, H, Hanly, A, Hasegawa, H, Iversen, LH, Hill, A, Hill, J, Hoch, J, Hoffmeister, M, Hompes, R, Hurtado, L, Iaquinandi, F, Imbrasaite, U, Islam, R, Jafari, MD, Kanemitsu, Y, Karachun, A, Karimuddin, AA, Keller, DS, Kelly, J, Kennelly, R, Khrykov, G, Kocian, P, Koh, C, Kok, N, Knight, KA, Knol, J, Kontovounisios, C, Korner, H, Krivokapic, Z, Kronberger, I, Kroon, HM, Kryzauskas, M, Kural, S, Kusters, M, Lakkis, Z, Lankov, T, Larson, D, Lazar, G, Lee, K-Y, Lee, SH, Lefevre, JH, Lepisto, A, Lieu, C, Loi, L, Lynch, C, Maillou-Martinaud, H, Maroli, A, Martin, S, Martling, A, Matzel, KE, Mayol, J, McDermott, F, Meurette, G, Millan, M, Mitteregger, M, Moiseenko, A, Monson, JRT, Morarasu, S, Moritani, K, Moslein, G, Munini, M, Nahas, C, Nahas, S, Negoi, I, Novikova, A, Ocares, M, Okabayashi, K, Olkina, A, Onate-Ocana, L, Otero, J, Ozen, C, Pace, U, Juliao, GPS, Panaiotti, L, Panis, Y, Papamichael, D, Park, J, Patel, S, Uriburu, JCP, Pera, M, Perez, RO, Petrov, A, Pfeffer, F, Phang, PT, Poskus, T, Pringle, H, Proud, D, Raguz, I, Rama, N, Rasheed, S, Raval, MJ, Rega, D, Reissfelder, C, Meneses, JCR, Ris, F, Riss, S, Rodriguez-Zentner, H, Roxburgh, CS, Saklani, A, Salido, AJ, Sammour, T, Saraste, D, Schneider, M, Seishima, R, Sekulic, A, Seppala, T, Sheahan, K, Shine, R, Shlomina, A, Sica, GS, Singnomklao, T, Siragusa, L, Smart, N, Solis, A, Spinelli, A, Staiger, RD, Stamos, MJ, Steele, S, Sunderland, M, Tan, K-K, Tanis, PJ, Tekkis, P, Teklay, B, Tengku, S, Jimenez-Toscano, M, Tsarkov, P, Turina, M, Ulrich, A, Vailati, BB, van Harten, M, Verhoef, C, Warrier, S, Wexner, S, de Wilt, H, Weinberg, BA, Wells, C, Wolthuis, A, Xynos, E, You, N, Zakharenko, A, Zeballos, J, and Winter, DC

Abstract

IMPORTANCE: The incidence of early-onset colorectal cancer (younger than 50 years) is rising globally, the reasons for which are unclear. It appears to represent a unique disease process with different clinical, pathological, and molecular characteristics compared with late-onset colorectal cancer. Data on oncological outcomes are limited, and sensitivity to conventional neoadjuvant and adjuvant therapy regimens appear to be unknown. The purpose of this review is to summarize the available literature on early-onset colorectal cancer. OBSERVATIONS: Within the next decade, it is estimated that 1 in 10 colon cancers and 1 in 4 rectal cancers will be diagnosed in adults younger than 50 years. Potential risk factors include a Westernized diet, obesity, antibiotic usage, and alterations in the gut microbiome. Although genetic predisposition plays a role, most cases are sporadic. The full spectrum of germline and somatic sequence variations implicated remains unknown. Younger patients typically present with descending colonic or rectal cancer, advanced disease stage, and unfavorable histopathological features. Despite being more likely to receive neoadjuvant and adjuvant therapy, patients with early-onset disease demonstrate comparable oncological outcomes with their older counterparts. CONCLUSIONS AND RELEVANCE: The clinicopathological features, underlying molecular profiles, and drivers of early-onset colorectal cancer differ from those of late-onset disease. Standardized, age-specific preventive, screening, diagnostic, and therapeutic strategies are required to optimize outcomes.

Published
2021

4. TreatmENT of AnastomotiC LeakagE after rectal cancer resection: the TENTACLE - Rectum study

Author

van Workum F, Talboom K, Hannink G, Wolthuis A, de Lacy FB, Lefevre JH, Solomon M, Frasson M, Rotholtz N, Denost Q, Perez RO, Konishi T, Rosman C, Hompes R, Tanis PJ, and de Wilt JH

Subjects
Anastomotic leakage, Rectal cancer, treatment, macromolecular substances
Abstract

Anastomotic Leakage is a severe complication after Low Anterior Resection (LAR) for rectal cancer and occurs in up to 20% of patients. Most research focusses on reducing incidence and predictive factors of anastomotic leakage. There are no robust data on severity and treatment strategies with associated outcomes.

Published
2020

5. Transanal total mesorectal excision: international registry results of the first 720 cases

Author

Penna M, Hompes R, Arnold S, Wynn G, Austin R, Warusavitarne J, Moran B, Hanna GB, Mortensen NJ, Tekkis PP, Albert M, Al Furajii H, Allison A, Arezzo A, Aryal K, Ashraf S, Atallah S, Baig K, Baral J, Bemelman W, Berger D, Boni L, Bonjer J, Bordeianou L, Borreca D, Buchs NC, Cahill R, Campbell K, Capolupo G, Caricato M, Cassinotti E, Chambers W, Courtney ED, Cunningham C, Dalton S, Dawson R, Delrio P, de Graaf E, De Paolis P, D'Hondt M, D'Hoore A, Doornebosch P, Erikson JR, Estevez-Schwarz L, Fabryko M, Fernandez-Hevia M, Forsmo H, Francis N, Garimella V, Gecim IE, Geissmann D, Gill K, Glockler M, Grieco M, Grolich T, Guy R, Hayes J, Hoffman TJ, Houben B, Ito M, Jelic F, Jones O, Joy H, Kala Z, Katory M, Kneist W, Knol J, Korsgen S, Kukreja N, Kunz R, Lacy A, Lal R, Lang H, La Vaccara V, Lezoche E, Lima MA, Mamedli Z, Mansfield S, Marsanic P, Mellano A, Mendes CRS, Merrie A, Miles A, Miroshnychenko Y, Morino M, Muratore A, Nicol D, Oh JH, O'Loughlin P, Pandey S, Paraoan M, Pei CFW, Perez RO, Pfeffer F, Picchetto A, Pockney P, Radley S, Rasulov A, Rega D, Ris F, Riss S, Sains P, Samarasinghe S, Juliao GPS, Seitinger G, Shaikh I, Sietses C, Sileri P, Fernandez VS, Smith S, Sohn DK, Speakman C, Stevenson A, Stift A, Sylla P, Tanis P, Teso EP, Tuech JJ, Tuynman J, van der Zaag E, van Duijvendijk P, Van Nieuwenhove Y, Vansteenkiste F, Velthuis S, Venkatsubramaniam A, Vorburger S, Wassenaar E, Wegstapel H, Wolthuis A, Wu L, Penna, M, Hompes, R, Arnold, S, Wynn, G, Austin, R, Warusavitarne, J, Moran, B, Hanna, Gb, Mortensen, Nj, Tekkis, Pp, Albert, M, Al Furajii, H, Allison, A, Arezzo, A, Aryal, K, Ashraf, S, Atallah, S, Baig, K, Baral, J, Bemelman, W, Berger, D, Boni, L, Bonjer, J, Bordeianou, L, Borreca, D, Buchs, Nc, Cahill, R, Campbell, K, Capolupo, G, Caricato, M, Cassinotti, E, Chambers, W, Courtney, Ed, Cunningham, C, Dalton, S, Dawson, R, Delrio, P, de Graaf, E, De Paolis, P, D'Hondt, M, D'Hoore, A, Doornebosch, P, Erikson, Jr, Estevez-Schwarz, L, Fabryko, M, Fernandez-Hevia, M, Forsmo, H, Francis, N, Garimella, V, Gecim, Ie, Geissmann, D, Gill, K, Glockler, M, Grieco, M, Grolich, T, Guy, R, Hayes, J, Hoffman, Tj, Houben, B, Ito, M, Jelic, F, Jones, O, Joy, H, Kala, Z, Katory, M, Kneist, W, Knol, J, Korsgen, S, Kukreja, N, Kunz, R, Lacy, A, Lal, R, Lang, H, La Vaccara, V, Lezoche, E, Lima, Ma, Mamedli, Z, Mansfield, S, Marsanic, P, Mellano, A, Mendes, Cr, Merrie, A, Miles, A, Miroshnychenko, Y, Morino, M, Muratore, A, Nicol, D, Oh, Jh, O'Loughlin, P, Pandey, S, Paraoan, M, Pei, Cfw, Perez, Ro, Pfeffer, F, Picchetto, A, Pockney, P, Radley, S, Rasulov, A, Rega, D, Ris, F, Riss, S, Sains, P, Samarasinghe, S, Juliao, Gp, Seitinger, G, Shaikh, I, Sietses, C, Sileri, P, Fernandez, V, Smith, S, Sohn, Dk, Speakman, C, Stevenson, A, Stift, A, Sylla, P, Tanis, P, Teso, Ep, Tuech, Jj, Tuynman, J, van der Zaag, E, van Duijvendijk, P, Van Nieuwenhove, Y, Vansteenkiste, F, Velthuis, S, Venkatsubramaniam, A, Vorburger, S, Wassenaar, E, Wegstapel, H, Wolthuis, A, Wu, L, Surgery, CCA - Cancer Treatment and quality of life, AGEM - Re-generation and cancer of the digestive system, CCA - Cancer Treatment and Quality of Life, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, and AGEM - Digestive immunity

Subjects
Male, SURGERY, medicine.medical_treatment, Anal Canal, registry, Body Mass Index, 0302 clinical medicine, Postoperative Complications, Risk Factors, PATHOLOGICAL OUTCOMES, Registries, Intraoperative Complications, Neoadjuvant therapy, Digestive System Surgical Procedures, 11 Medical and Health Sciences, Aged, 80 and over, education.field_of_study, Anal canal, Middle Aged, Total mesorectal excision, Neoadjuvant Therapy, RANDOMIZED CLINICAL-TRIAL, Dissection, medicine.anatomical_structure, Treatment Outcome, transanal total mesorectal excision, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, Life Sciences & Biomedicine, Adult, medicine.medical_specialty, Adolescent, Population, Perforation (oil well), LOW-RECTAL-CANCER, Rectum, 03 medical and health sciences, Young Adult, medicine, Humans, Minimally Invasive Surgical Procedures, education, rectal cancer, MARGIN INVOLVEMENT, Mesorectal, Aged, Neoplasm Staging, Science & Technology, poor histological outcomes, LAPAROSCOPIC-ASSISTED RESECTION, business.industry, Rectal Neoplasms, TaTME Registry Collaborative, Surgery, Surgery, poor histological outcomes, rectal cancer, registry, risk factors, transanal total mesorectal excision, business
Abstract

OBJECTIVE: This study aims to report short-term clinical and oncological outcomes from the international transanal Total Mesorectal Excision (taTME) registry for benign and malignant rectal pathology. BACKGROUND: TaTME is the latest minimally invasive transanal technique pioneered to facilitate difficult pelvic dissections. Outcomes have been published from small cohorts, but larger series can further assess the safety and efficacy of taTME in the wider surgical population. METHODS: Data were analyzed from 66 registered units in 23 countries. The primary endpoint was "good-quality TME surgery." Secondary endpoints were short-term adverse events. Univariate and multivariate regression analyses were used to identify independent predictors of poor specimen outcome. RESULTS: A total of 720 consecutively registered cases were analyzed comprising 634 patients with rectal cancer and 86 with benign pathology. Approximately, 67% were males with mean BMI 26.5 kg/m. Abdominal or perineal conversion was 6.3% and 2.8%, respectively. Intact TME specimens were achieved in 85%, with minor defects in 11% and major defects in 4%. R1 resection rate was 2.7%. Postoperative mortality and morbidity were 0.5% and 32.6% respectively. Risk factors for poor specimen outcome (suboptimal TME specimen, perforation, and/or R1 resection) on multivariate analysis were positive CRM on staging MRI, low rectal tumor CONCLUSIONS: TaTME appears to be an oncologically safe and effective technique for distal mesorectal dissection with acceptable short-term patient outcomes and good specimen quality. Ongoing structured training and the upcoming randomized controlled trials are needed to assess the technique further.

Published
2017
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6. Long-term outcomes of clinical complete responders after neoadjuvant treatment for rectal cancer in the International Watch & Wait Database (IWWD): an international multicentre registry study

Author

van der Valk, MJM, Hilling, DE, Bastiaannet, E, Meershoek-Klein Kranenbarg, E, Beets, GL, Figueiredo, NL, Habr-Gama, A, Perez, RO, Renehan, AG, van de Velde, CJH, IWWD Consortium, Ahlberg, M, Appelt, A, Asoglu, O, Bär, M-T, Barroca, R, Beets-Tan, RGH, Belgers, EHJ, Bosker, RJI, Breukink, SO, Bujko, K, Carvalho, C, Cunningham, C, Creavin, B, D'Hoore, A, Gérard, J-P, Gollins, S, Hoff, C, Holman, FA, Hupkens, BJP, Iseas, S, Jakobsen, A, Keshvari, A, Koopal, SA, Kusters, M, Langheinrich, M, Leijtens, JWA, Maas, M, Malcomson, L, Mamedli, ZZ, Martling, A, Matzel, KE, Melenhorst, J, Morici, ML, Murad-Regadas, SM, O'Dwyer, ST, Peeters, KCMJ, Rosa, I, Rossi, G, Rutten, HJT, Sanchez Loria, F, van der Sande, ME, São Julião, GP, Saunders, M, Sun Myint, A, van der Sluis, H, Schiappa, R, Scott, N, Stoot, JHMB, Talsma, AK, Terrasson, I, Tokmak, H, Vaccaro, CA, Vahrmeijer, AL, Wasowicz, DK, Westreenen, HL, Winter, DC, Wolthuis, AM, and Zimmerman, DDE

Abstract

Background: The strategy of watch and wait (W&W) in patients with rectal cancer who achieve a complete clinical response (cCR) after neoadjuvant therapy is new and offers an opportunity for patients to avoid major resection surgery. However, evidence is based on small-to-moderate sized series from specialist centres. The International Watch & Wait Database (IWWD) aims to describe the outcome of the W&W strategy in a large-scale registry of pooled individual patient data. We report the results of a descriptive analysis after inclusion of more than 1000 patients in the registry. Methods: Participating centres entered data in the registry through an online, highly secured, and encrypted research data server. Data included baseline characteristics, neoadjuvant therapy, imaging protocols, incidence of local regrowth and distant metastasis, and survival status. All patients with rectal cancer in whom the standard of care (total mesorectal excision surgery) was omitted after neoadjuvant therapy were eligible to be included in the IWWD. For the present analysis, we only selected patients with no signs of residual tumour at reassessment (a cCR). We analysed the proportion of patients with local regrowth, proportion of patients with distant metastases, 5-year overall survival, and 5-year disease-specific survival. Findings: Between April 14, 2015, and June 30, 2017, we identified 1009 patients who received neoadjuvant treatment and were managed by W&W in the database from 47 participating institutes (15 countries). We included 880 (87%) patients with a cCR. Median follow-up time was 3·3 years (95% CI 3·1–3·6). The 2-year cumulative incidence of local regrowth was 25·2% (95% CI 22·2–28·5%), 88% of all local regrowth was diagnosed in the first 2 years, and 97% of local regrowth was located in the bowel wall. Distant metastasis were diagnosed in 71 (8%) of 880 patients. 5-year overall survival was 85% (95% CI 80·9–87·7%), and 5-year disease-specific survival was 94% (91–96%). Interpretation: This dataset has the largest series of patients with rectal cancer treated with a W&W approach, consisting of approximately 50% data from previous cohort series and 50% unpublished data. Local regrowth occurs mostly in the first 2 years and in the bowel wall, emphasising the importance of endoscopic surveillance to ensure the option of deferred curative surgery. Local unsalvageable disease after W&W was rare. Funding: European Registration of Cancer Care financed by European Society of Surgical Oncology, Champalimaud Foundation Lisbon, Bas Mulder Award granted by the Alpe d'Huzes Foundation and Dutch Cancer Society, and European Research Council Advanced Grant.

Published
2018

8. Individual participant data pooled-analysis of risk factors for recurrence after neoadjuvant radiotherapy and transanal local excision of rectal cancer: the PARTTLE study.

Author

Arezzo, A, Lo Secco, G, Passera, R, Esposito, L, Guerrieri, M, Ortenzi, M, Bujko, K, Perez, Ro, Habr-Gama, A, Stipa, F, Picchio, M, Restivo, A, Zorcolo, L, Coco, Claudio, Rizzo, Gianluca, Mistrangelo, M, Morino, M., Coco C (ORCID:0000-0002-4713-7093), Rizzo G, Arezzo, A, Lo Secco, G, Passera, R, Esposito, L, Guerrieri, M, Ortenzi, M, Bujko, K, Perez, Ro, Habr-Gama, A, Stipa, F, Picchio, M, Restivo, A, Zorcolo, L, Coco, Claudio, Rizzo, Gianluca, Mistrangelo, M, Morino, M., Coco C (ORCID:0000-0002-4713-7093), and Rizzo G

Abstract

BACKGROUND: An organ-preserving strategy may be a valid alternative in the treatment of selected patients with rectal cancer after neoadjuvant radiotherapy. Preoperative assessment of the risk for tumor recurrence is a key component of surgical planning. The aim of the present study was to increase the current knowledge on the risk factors for tumor recurrence. METHODS: The present study included individual participant data of published studies on rectal cancer surgery. The literature was reviewed according to according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Individual Participant Data checklist (PRISMA-IPD) guidelines. Series of patients, whose data were collected prospectively, having neoadjuvant radiotherapy followed by transanal local excision for rectal cancer were reviewed. Three independent series of univariate/multivariate binary logistic regression models were estimated for the risk of local, systemic and overall recurrence, respectively. RESULTS: We identified 15 studies, and 7 centers provided individual data on 517 patients. The multivariate analysis showed higher local and overall recurrences for ypT3 stage (OR 4.79; 95% CI 2.25-10.16 and OR 6.43 95% CI 3.33-12.42), tumor size after radiotherapy > 10 mm (OR 5.86 95% CI 2.33-14.74 and OR 3.14 95% CI 1.68-5.87), and lack of combined chemotherapy (OR 3.68 95% CI 1.78-7.62 and OR 2.09 95% CI 1.10-3.97), while ypT3 was the only factor correlated with systemic recurrence (OR 5.93). The analysis of survival curves shows that the overall survival is associated with ypT and not with cT. CONCLUSIONS: Local excision should be offered with caution after neoadjuvant chemoradiotherapy to selected patients with rectal cancers, who achieved a good response to neoadjuvant chemoradiotherapy.

Published
2019

10. Session 4: Trying to augment response with chemotherapy: a triumph of hope over experience?

Author

Battersby, NJ, Perez, RO, Baxter, N, Moran, B, Brown, G, Battersby, NJ, Perez, RO, Baxter, N, Moran, B, and Brown, G

Abstract

As part of an approach to improve tumour regression and increase the proportion of patients with complete clinical and radiological response, Dr Perez reviews the methods and evidence base for augmenting therapy and thus augmenting response rates preoperatively. Much of the data reviewed were in the context of patients undergoing a watch-and-wait approach for rectal cancer after initial treatment with chemoradiotherapy.

Published
2018

17. Mutational analysis of genes coding for cell surface proteins in colorectal cancer cell lines reveal novel altered pathways, druggable mutations and mutated epitopes for targeted therapy

Author

Donnard, E, Asprino, PF, Correa, BR, Bettoni, F, Koyama, FC, Navarro, FCP, Perez, RO, Mariadason, J, Sieber, OM, Strausberg, RL, Simpson, AJG, Jardim, DLF, Reis, LFL, Parmigiani, RB, Galante, PAF, Camargo, AA, Donnard, E, Asprino, PF, Correa, BR, Bettoni, F, Koyama, FC, Navarro, FCP, Perez, RO, Mariadason, J, Sieber, OM, Strausberg, RL, Simpson, AJG, Jardim, DLF, Reis, LFL, Parmigiani, RB, Galante, PAF, and Camargo, AA

Abstract

We carried out a mutational analysis of 3,594 genes coding for cell surface proteins (Surfaceome) in 23 colorectal cancer cell lines, searching for new altered pathways, druggable mutations and mutated epitopes for targeted therapy in colorectal cancer. A total of 3,944 somatic non-synonymous substitutions and 595 InDels, occurring in 2,061 (57%) Surfaceome genes were catalogued. We identified 48 genes not previously described as mutated in colorectal tumors in the TCGA database, including genes that are mutated and expressed in >10% of the cell lines (SEMA4C, FGFRL1, PKD1, FAM38A, WDR81, TMEM136, SLC36A1, SLC26A6, IGFLR1). Analysis of these genes uncovered important roles for FGF and SEMA4 signaling in colorectal cancer with possible therapeutic implications. We also found that cell lines express on average 11 druggable mutations, including frequent mutations (>20%) in the receptor tyrosine kinases AXL and EPHA2, which have not been previously considered as potential targets for colorectal cancer. Finally, we identified 82 cell surface mutated epitopes, however expression of only 30% of these epitopes was detected in our cell lines. Notwithstanding, 92% of these epitopes were expressed in cell lines with the mutator phenotype, opening new venues for the use of "general" immune checkpoint drugs in this subset of patients.

Published
2014

25. A Pharmacist and Health Coach–Delivered Mobile Health Intervention for Type 2 Diabetes: Protocol for a Randomized Controlled Crossover Study

Author

Sharp, Lisa Kay, Biggers, Alana, Perez, Rosanne, Henkins, Julia, Tilton, Jessica, and Gerber, Ben S

Subjects
Medicine, Computer applications to medicine. Medical informatics, R858-859.7
Abstract

BackgroundAggressive management of blood glucose, blood pressure, and cholesterol through medication and lifestyle adherence is necessary to minimize the adverse health outcomes of type 2 diabetes. However, numerous psychosocial and environmental barriers to adherence prevent low-income, urban, and ethnic minority populations from achieving their management goals, resulting in diabetes complications. Health coaches working with clinical pharmacists represent a promising strategy for addressing common diabetes management barriers. Mobile health (mHealth) tools may further enhance their ability to support vulnerable minority populations in diabetes management. ObjectiveThe aim of this study is to evaluate the impact of an mHealth clinical pharmacist and health coach–delivered intervention on hemoglobin A1c (HbA1c, primary outcome), blood pressure, and low-density lipoprotein (secondary outcomes) in African-Americans and Latinos with poorly controlled type 2 diabetes. MethodsA 2-year, randomized controlled crossover study will evaluate the effectiveness of an mHealth diabetes intervention delivered by a health coach and clinical pharmacist team compared with usual care. All patients will receive 1 year of team intervention, including lifestyle and medication support delivered in the home with videoconferencing and text messages. All patients will also receive 1 year of usual care without team intervention and no home visits. The order of the conditions received will be randomized. Our recruitment goal is 220 urban African-American or Latino adults with uncontrolled type 2 diabetes (HbA1c ≥8%) receiving care from a largely minority-serving, urban academic medical center. The intervention includes the following: health coaches supporting patients through home visits, phone calls, and text messaging and clinical pharmacists supporting patients through videoconferences facilitated by health coaches. Data collection includes physiologic (HbA1c, blood pressure, weight, and lipid profile) and survey measures (medication adherence, diabetes-related behaviors, and quality of life). Data collection during the second year of study will determine the maintenance of any physiological improvement among participants receiving the intervention during the first year. ResultsParticipant enrollment began in March 2017. We have recruited 221 patients. Intervention delivery and data collection will continue until November 2021. The results are expected to be published by May 2022. ConclusionsThis is among the first trials to incorporate health coaches, clinical pharmacists, and mHealth technologies to increase access to diabetes support among urban African-Americans and Latinos to achieve therapeutic goals. International Registered Report Identifier (IRRID)DERR1-10.2196/17170

Published
2021
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26. Índice de Figuras

Author

Pérez, Rosana, Arenas, Favián E., Martínez, Héctor J., and Arias, Carlos A.

Published
2019

27. Contenido

Author

Pérez, Rosana, Arenas, Favián E., Martínez, Héctor J., and Arias, Carlos A.

Published
2019

31. Prefacio

Author

Pérez, Rosana, Arenas, Favián E., Martínez, Héctor J., and Arias, Carlos A.

Published
2019

32. Índice de Tablas

Author

Pérez, Rosana, Arenas, Favián E., Martínez, Héctor J., and Arias, Carlos A.

Published
2019

36. Bibliografía

Author

Pérez, Rosana, Arenas, Favián E., Martínez, Héctor J., and Arias, Carlos A.

Published
2019

37. Capítulo 5 Aplicaciones

Author

Pérez, Rosana, Arenas, Favián E., Martínez, Héctor J., and Arias, Carlos A.

Published
2019

39. Índice Alfabético

Author

Pérez, Rosana, Arenas, Favián E., Martínez, Héctor J., and Arias, Carlos A.

Published
2019

43. Accuracy of positron emission tomography/computed tomography and clinical assessment in the detection of complete rectal tumor regression after neoadjuvant chemoradiation: long-term results of a prospective trial (National Clinical Trial 00254683).

Author

Perez RO, Habr-Gama A, Gama-Rodrigues J, Proscurshim I, Juliao GP, Lynn P, Ono CR, Campos FG, Silva e Sousa AH Jr, Imperiale AR, Nahas SC, Buchpiguel CA, Perez, Rodrigo Oliva, Habr-Gama, Angelita, Gama-Rodrigues, Joaquim, Proscurshim, Igor, Julião, Guilherme Pagin São, Lynn, Patricio, Ono, Carla Rachel, and Campos, Fabio Guilherme

Abstract

Background: Neoadjuvant chemoradiation (CRT) therapy may result in significant tumor regression in patients with rectal cancer. Patients who develop complete tumor regression have been managed by treatment strategies that are alternatives to standard total mesorectal excision. Therefore, assessment of tumor response with positron emission tomography/computed tomography (PET/CT) after neoadjuvant treatment may offer relevant information for the selection of patients to receive alternative treatment strategies. Methods: Patients with clinical T2 (cT2) through cT4NxM0 rectal adenocarcinoma were included prospectively. Neoadjuvant therapy consisted of 54 grays of radiation and 5-fluorouracil-based chemotherapy. Baseline PET/CT studies were obtained before CRT followed by PET/CT studies at 6 weeks and 12 weeks after the completion of CRT. Clinical assessment was performed at 12 weeks after CRT completion. PET/CT results were compared with clinical and pathologic data. Results: In total, 99 patients were included in the study. Twenty-three patients were complete responders (16 had a complete clinical response, and 7 had a complete pathologic response). The PET/CT response evaluation at 12 weeks indicated that 18 patients had a complete response, and 81 patients had an incomplete response. There were 5 false-negative and 10 false-positive PET/CT results. PET/CT for the detection of residual cancer had 93% sensitivity, 53% specificity, a 73% negative predictive value, an 87% positive predictive value, and 85% accuracy. Clinical assessment alone resulted in an accuracy of 91%. PET/CT information may have detected misdiagnoses made by clinical assessment alone, improving overall accuracy to 96%. Conclusions: Assessment of tumor response at 12 weeks after CRT completion with PET/CT imaging may provide a useful additional tool with good overall accuracy for the selection of patients who may avoid unnecessary radical resection after achieving a complete clinical response. Cancer 2012;3501-3511. © 2011 American Cancer Society. [ABSTRACT FROM AUTHOR]

Published
2012
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