Incomplete cytoreductive surgery for appendiceal and colorectal peritoneal carcinomatosis: Characteristics and outcomes of an overlooked group.

BACKGROUND OND OBJECTIVES: Complete cytoreductive surgery (CRS) may prolong survival for selected patients with peritoneal carcinomatosis from colorectal cancer (CRC). However, there is a paucity of data on outcomes following incomplete procedures. METHODS: Patients with incomplete CRS for well-differentiated (WD) and moderate/poorly-differentiated (M/PD) appendiceal cancer, right and left CRC were identified at a single tertiary center (2008-2021). RESULTS: Of 109 patients, 10% were WD and 51% M/PD appendiceal cancers, and 16% right and 23% left CRC. There were no differences in gender, BMI (mean = 27), ASA score, previous abdominal surgery (72%), and extent of CRS. The PC Index differed between appendiceal and colorectal cancers (mean = 27 vs. 17, p < 0.01). Overall, the perioperative outcomes were similar among the groups, with 15% experiencing complications. Postoperatively, 61% received chemotherapy, and 51% required ≥1 subsequent procedure. The 1 and 3-year survival for the WD, M/PD, right and left CRC subgroups were 100%, 67%, 44%, 51%, and 88%, 17%, 12%, and 23%, respectively (p = 0.02). CONCLUSIONS: Incomplete CRS was associated with significant morbidity and number of subsequent palliative procedures. Prognosis correlated with histologic subtype; WD appendiceal cancer patients having superior outcomes, while those with right sided CRC the worst survival. These data may help guiding expectations in the setting of incomplete procedures.

Assessment of Patient-Reported Outcomes in Patients With Anal Squamous-Cell Cancer Undergoing Combined Modality Therapy.

BACKGROUND: There is limited knowledge on long-term bowel, sexual, and urinary function after combined modality therapy for anal squamous-cell cancer. OBJECTIVE: This study aimed to evaluate long-term changes in patients treated with combined modality. DESIGN: This was a retrospective study of prospectively collected patient-reported outcome surveys. SETTING: This study was conducted at a single institution. PATIENTS: There were 143 patients with stage I to III anal cancer who were treated with chemoradiation and had completed the survey. MAIN OUTCOME MEASURES: This study included patient-reported outcomes reflecting bowel, sexual, and urinary function. RESULTS: Thirty-nine percent of patients had major low anterior resection syndrome at baseline. Major low anterior resection syndrome remained stable (38%; 95% CI, 31%-46%) with no change over time (OR 0.95; 95% CI, 0.74-1.21; p = 0.7). Higher rates of major low anterior resection syndrome were observed for patients who had major low anterior resection syndrome at baseline (OR 20.7; 95% CI 4.70-91.3; p < 0.001) and for females (OR 2.14; 95% CI, 1.01-4.56; p = 0.047). On 5-point scales, we saw a nonsignificant increased level of sexual arousal during sexual activity after therapy for women (ß for 1 year = 0.15; 95% CI, -0.01 to 0.32; p = 0.072) and nonsignificant decreased confidence in getting and keeping an erection after therapy for men (ß for 1 year = -0.33; 95% CI, -0.66 to 0.00; p = 0.053). LIMITATIONS: This was a single-institution study and only patients who answered the questionnaire were included in the study. CONCLUSIONS: A significant proportion of patients have major low anterior resection syndrome at baseline and after successful treatment for anal cancer. Having major low anterior resection syndrome at baseline was the biggest predictor of having major low anterior resection syndrome after treatment. Bowel, sexual, and urinary function did not improve over time up to 2 years after end of treatment. Physicians should counsel their patients before treatment that baseline poor bowel function is a risk factor for posttreatment bowel dysfunction. See Video Abstract at http://links.lww.com/DCR/C29 . EVALUACIN DE LOS RESULTADOS INFORMADOS POR LOS PACIENTES CON CNCER ANAL DE CLULAS ESCAMOSAS QUE SE SOMETEN A UNA TERAPIA DE MODALIDAD COMBINADA: ANTECEDENTES:Existe un conocimiento limitado sobre la función intestinal, sexual y urinaria a largo plazo después de la terapia de modalidad combinada para el cáncer anal de células escamosas.OBJETIVO:Evaluar los cambios a largo plazo en la función intestinal, sexual y urinaria en pacientes tratados con modalidad combinada.DISEÑO:Este fue un estudio retrospectivo de encuestas de resultados informadas por pacientes recolectadas prospectivamente.ESCENARIO:Institución única.PACIENTES:Fueron 143 pacientes con cáncer anal en estadio I-III que fueron tratados con quimiorradiación y completaron la encuesta.PRINCIPALES MEDIDAS DE RESULTADO:Resultados reportados por el paciente que reflejan la función intestinal, sexual, y urinaria.RESULTADOS:Treinta y nueve por ciento de los pacientes tenían puntajes importantes de síndrome de resección anterior bajo al inicio del estudio. Las puntuaciones del síndrome de resección anterior baja mayor permanecieron estables (38 %; IC del 95%: 31 %, 46 %) sin cambios con el tiempo (OR 0,95, IC del 95%: 0,74, 1,21, p = 0,7). Se observaron tasas más altas de puntuaciones del síndrome de resección anterior baja mayor para los pacientes que tenían puntuaciones del síndrome de resección anterior baja mayor desde el inicio (OR 20,7; IC del 95%: 4,70; 91,3, p < 0,001) y para las mujeres (OR 2,14; IC del 95%: 1,01, 4,56; p = 0,047). En escalas de 5 puntos, observamos un aumento no significativo del nivel de excitación sexual durante la actividad sexual después de la terapia para las mujeres (ß durante 1 año = 0,15; IC del 95%: -0,01, 0,32; p = 0,072) y una disminución no significativa de la confianza en lograr y mantener una erección después de la terapia para hombres (ß para 1 año = -0,33; IC del 95%: -0,66, 0,00; p = 0,053).LIMITACIONES:Este es un estudio de una sola institución. Solo se incluyeron en el estudio los pacientes que contestaron el cuestionario.CONCLUSIONES:Una proporción significativa de pacientes tienen puntajes de síndrome de resección anterior muy bajos al inicio del estudio y después de un tratamiento exitoso para el cáncer anal. Tener puntajes de síndrome de resección anterior bajos importantes al inicio del estudio fue el predictor más importante de tener puntajes de síndrome de resección anterior bajos importantes después del tratamiento. La función intestinal, sexual y urinaria no mejoró con el tiempo hasta 2 años después de finalizar el tratamiento. Los médicos deben aconsejar a sus pacientes antes del tratamiento que la mala función intestinal inicial es un factor de riesgo para la disfunción intestinal posterior al tratamiento. Consulte Video Resumen en http://links.lww.com/DCR/C29 . (Traducción-Dr. Yolanda Colorado ).

Mediator kinase inhibition impedes transcriptional plasticity and prevents resistance to ERK/MAPK-targeted therapy in KRAS-mutant cancers.

Acquired resistance remains a major challenge for therapies targeting oncogene activated pathways. KRAS is the most frequently mutated oncogene in human cancers, yet strategies targeting its downstream signaling kinases have failed to produce durable treatment responses. Here, we developed multiple models of acquired resistance to dual-mechanism ERK/MAPK inhibitors across KRAS-mutant pancreatic, colorectal, and lung cancers, and then probed the long-term events enabling survival against this class of drugs. These studies revealed that resistance emerges secondary to large-scale transcriptional adaptations that are diverse and cell line-specific. Transcriptional reprogramming extends beyond the well-established early response, and instead represents a dynamic, evolved process that is refined to attain a stably resistant phenotype. Mechanistic and translational studies reveal that resistance to dual-mechanism ERK/MAPK inhibition is broadly susceptible to manipulation of the epigenetic machinery, and that Mediator kinase, in particular, can be co-targeted at a bottleneck point to prevent diverse, cell line-specific resistance programs.

Effect of Neoadjuvant Systemic Chemotherapy With or Without Chemoradiation on Bowel Function in Rectal Cancer Patients Treated With Total Mesorectal Excision.

BACKGROUND: Neoadjuvant chemoradiation (CRT) impairs bowel function in patients with rectal cancer treated with total mesorectal excision (TME). The impact of other forms of neoadjuvant therapy such as neoadjuvant chemotherapy alone (NC) and induction chemotherapy followed by CRT (total neoadjuvant therapy or TNT) on postoperative bowel function has not been investigated. METHODS: We conducted a retrospective review of 176 rectal cancer patients treated between November 1, 2011, and August 31, 2017. All patients completed the MSKCC Bowel Function Instrument (BFI), a validated bowel function questionnaire, at least 6 months after TME and/or ileostomy reversal. Differences in BFI scores were compared across four groups (surgery alone, CRT, NC, and TNT) and also according to exposure to neoadjuvant RT and neoadjuvant chemotherapy. A multivariable linear regression model was used to evaluate the independent relationship between exposure to neoadjuvant RT or chemotherapy and BFI. RESULTS: BFI total scores were significantly different between the four groups (p = 0.008). Exposure to RT correlated with worse BFI total scores (p = 0.002), and no differences were found in BFI total score after exposure to neoadjuvant chemotherapy (p = 0.92). In a linear regression model, only exposure to RT (ß = - 5.1; 95% CI - 8.9 to - 1.3; p = 0.008) and tumor distance from the anal verge (ß = 1.23; 95% CI 0.48 to 1.97; p = 0.001) were significantly correlated with BFI total score. CONCLUSION: NC, whether administered alone or added to CRT, does not seem to impair bowel function. These data should be used to counsel rectal cancer patients when discussing neoadjuvant therapy options.