Publications by authors named "Leonard Saltz"

Article Synopsis
  • Total mesorectal excision with intersphincteric resection and handsewn coloanal anastomosis (ISR-CAA) is considered safe for patients with distal rectal cancer, but the outcomes for those not qualifying for a watch-and-wait strategy have yet to be studied.
  • A retrospective analysis compared ISR-CAA with abdominoperineal resection (APR) in patients who received neoadjuvant therapy, showing similar tumor characteristics but differing local recurrence rates.
  • Results revealed a lower 5-year local recurrence-free survival rate for ISR-CAA (79%) compared to APR (93%), while disease-free survival rates were similar for both groups.
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  • Current treatment options are limited by the expectation that alternative therapies must be proven "non-inferior" to existing ones, making trials expensive and complex.
  • Non-inferiority trials often overlook important factors like variability in treatment outcomes and place excessive burdens of proof on alternatives, especially in terms of toxicity and cost.
  • The authors suggest moving away from labeling trials as superiority or non-inferiority, advocating instead for a simpler description of trials as "comparative" to promote better patient-centered treatment options.
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  • Hepatic artery infusion (HAI) chemotherapy combined with systemic treatment shows promising long-term results for patients with intrahepatic cholangiocarcinoma (IHC), suggesting improved disease control and overall survival rates.
  • A phase II clinical trial and a retrospective analysis revealed a median progression-free survival (PFS) of 11.8 months and overall survival (OS) of 26.8 months among a subset of patients, with particular genomic alterations indicating worse outcomes.
  • The study indicates that HAI with floxuridine (FUDR) alongside systemic therapies can provide durable disease control in locally advanced IHC, while molecular changes, particularly in the TP53 pathway, might help predict patient response to treatment.
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Background: Total neoadjuvant therapy (TNT) has been used for patients with locally advanced rectal cancer. The optimal sequence of chemoradiotherapy (CRT) and chemotherapy (CT) is a matter of debate.

Methods: We performed a pooled analysis of the CAO/ARO/AIO-12 and OPRA multicenter, randomized phase 2 trials to identify patient subsets that could benefit from one TNT sequence over the other regarding disease-free survival (DFS).

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Article Synopsis
  • - Determining the best treatment plan for rectal cancer is complicated, involving choices between curative or palliative surgery and considering impact on bowel function and quality of life, especially for distal rectal cancer patients.
  • - Patients with rectal cancer face a higher risk of pelvic recurrence compared to those with colon cancer, making careful patient selection and a multidisciplinary treatment approach essential for better outcomes.
  • - Recent updates to the NCCN Guidelines for Rectal Cancer include new treatment options like endoscopic submucosal dissection for early cases, revisions to the total neoadjuvant therapy strategy, and a nonoperative "watch-and-wait" option for patients who respond well to initial therapy.
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  • Adenosquamous carcinoma (ASC) is a rare and severe form of colon cancer that often presents at more advanced stages compared to common adenocarcinomas, resulting in worse outcomes.
  • A study reviewed 13 cases of colonic ASC from 2000 to 2020, revealing that most patients were diagnosed at Stage III or IV, with a median age of 48.7 years and a high recurrence rate (53.8%).
  • The overall five-year survival rate for these patients was found to be only 38.5%, highlighting the need for further research to understand and improve management strategies.
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Background: Neoadjuvant therapy leads to a clinical complete response in a considerable proportion of patients with locally advanced rectal cancer, allowing for possible nonoperative management. The presence of mucin on magnetic resonance imaging (MRI) after neoadjuvant therapy leads to uncertainty about residual disease and appropriateness of a watch-and-wait strategy in patients with no evidence of disease on proctoscopy (endoscopic clinical complete response).

Methods: MRI reports for locally advanced rectal cancer patients seen between July 2016 and January 2020 at Memorial Sloan Kettering Cancer Center were queried for presence of mucin in the tumor bed on MRI following neoadjuvant therapy.

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  • * Results showed that NLM patients generally had better overall survival (OS) and progression-free survival (PFS) than LM patients in first-line and second-line chemotherapy, while OR rates were higher for LM patients overall.
  • * The findings indicate that LM serves as a negative prognostic factor in mCRC, supporting its use in stratifying patients in future clinical trials.
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  • Colorectal cancer (CRC) ranks as the fourth most common cancer and the second deadliest in the U.S.
  • Treatment for advanced metastatic CRC includes multiple active drugs used alone or in combination, depending on patient-specific factors.
  • The paper reviews the systemic therapy recommendations for metastatic CRC as outlined in the NCCN Guidelines for Colon Cancer.
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Background: Palmar-plantar erythrodysesthesia (PPE) is a slowly developing cutaneous reaction commonly experienced by patients treated with fluoropyrimidines. While erythrodysesthesia normally presents in a palmar-plantar distribution, it can also present with genital involvement, but this presentation is likely underreported and incorrectly attributed to an acute reaction from radiation therapy. This article aims to define erythrodysesthesia of the penis and scrotum as a rare but significant side effect of capecitabine.

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While epigenomic alterations are common in colorectal cancers (CRC), few epigenomic biomarkers that risk-stratify patients have been identified. We thus sought to determine the potential of promoter hypermethylation (m) as a prognostic and predictive marker in colon cancer. We examined the association of m with clinicopathologic features, relapse, survival, and treatment efficacy in patients with stage III colon cancer treated within a randomized adjuvant chemotherapy trial (CALGB/Alliance89803).

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Background: Oncologists are prescribing checkpoint inhibitors with greater frequency, and an awareness of and ability to recognize immune-related adverse events (irAEs) is a key part of the safe administration of these drugs.

Case Description: Herein, we report the case of a 26-year-old male diagnosed with metastatic right-sided colon cancer to the liver, with tumor immunohistochemistry demonstrating loss of and , and a pathogenic mutation in identified on germline testing, consistent with Lynch Syndrome. The patient received first-line treatment with pembrolizumab.

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Article Synopsis
  • - The OPRA trial studied the long-term outcomes of different treatment sequences for stage II/III rectal cancer, comparing induction chemotherapy followed by chemoradiation (INCT-CRT) with chemoradiation followed by consolidation chemotherapy (CRT-CNCT) to evaluate organ preservation and oncologic results.
  • - After a median follow-up of 5.1 years with 324 patients, the 5-year disease-free survival (DFS) rates were similar for both treatment groups, while TME-free survival was significantly higher in the CRT-CNCT group (54% vs. 39%).
  • - The study found that most tumor regrowth occurred within the first 2 years for patients who opted for the watch-and-w
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Metastatic and localized mismatch repair-deficient (dMMR) tumors are exquisitely sensitive to immune checkpoint blockade (ICB). The ability of ICB to prevent dMMR malignant or pre-malignant neoplasia development in patients with Lynch syndrome (LS) is unknown. Of 172 cancer-affected patients with LS who had received ≥1 ICB cycles, 21 (12%) developed subsequent malignancies after ICB exposure, 91% (29/32) of which were dMMR, with median time to development of 21 months (interquartile range, 6-38).

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Unlabelled: Metastatic colorectal cancer (mCRC) is a heterogeneous disease that can evoke discordant responses to therapy among different lesions in individual patients. The Response Evaluation Criteria in Solid Tumors (RECIST) criteria do not take into consideration response heterogeneity. We explored and developed lesion-based measurement response criteria to evaluate their prognostic effect on overall survival (OS).

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Purpose: Patients with locally advanced rectal cancer treated with total neoadjuvant therapy (TNT) may achieve organ preservation without a compromise to oncologic outcomes. However, reports on patient compliance with TNT and with treatment-related toxicities are limited.

Methods And Materials: The OPRA trial assessed organ preservation rates and oncologic outcomes in patients with clinical stage II/III rectal adenocarcinoma randomized to induction chemotherapy followed by chemoradiation (INCT-CRT) or chemoradiation followed by consolidation chemotherapy (CRT-CNCT).

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The optimal management of locally advanced rectal cancer is rapidly evolving. The National Cancer Institute Rectal-Anal Task Force convened an expert panel to develop consensus on the design of future clinical trials of patients with rectal cancer. A series of 82 questions and subquestions, which addressed radiation and neoadjuvant therapy, patient perceptions, rectal cancer populations of special interest, and unique design elements, were subject to iterative review using a Delphi analytical approach to define areas of consensus and those in which consensus is not established.

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Purpose: To evaluate the efficacy and safety of bevacizumab when added to first-line oxaliplatin-based chemotherapy (either capecitabine plus oxaliplatin [XELOX] or fluorouracil/folinic acid plus oxaliplatin [FOLFOX-4]) in patients with metastatic colorectal cancer (MCRC).

Patients And Methods: Patients with MCRC were randomly assigned, in a 2 × 2 factorial design, to XELOX versus FOLFOX-4, and then to bevacizumab versus placebo. The primary end point was progression-free survival (PFS).

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Article Synopsis
  • The NCCN Clinical Practice Guidelines outline the management of squamous cell anal carcinoma, emphasizing a multidisciplinary approach involving various medical specialties.
  • Primary treatment for anal and perianal cancers typically involves chemoradiation, and regular follow-ups are crucial for detecting any recurrence.
  • Recent updates to the guidelines have refined staging classifications and systemic therapy recommendations based on new research, improving treatment strategies for metastatic anal carcinoma.
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Background: Pelvic radiation plus sensitizing chemotherapy with a fluoropyrimidine (chemoradiotherapy) before surgery is standard care for locally advanced rectal cancer in North America. Whether neoadjuvant chemotherapy with fluorouracil, leucovorin, and oxaliplatin (FOLFOX) can be used in lieu of chemoradiotherapy is uncertain.

Methods: We conducted a multicenter, unblinded, noninferiority, randomized trial of neoadjuvant FOLFOX (with chemoradiotherapy given only if the primary tumor decreased in size by <20% or if FOLFOX was discontinued because of side effects) as compared with chemoradiotherapy.

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Article Synopsis
  • The study compares two treatment options for locally advanced rectal cancer: neoadjuvant FOLFOX (chemotherapy) and 5FUCRT (chemoradiation), focusing on patient experiences and outcomes.
  • A multicenter trial enrolled 1,194 patients, with 940 providing data on symptoms and quality of life before and after treatment.
  • Results showed that FOLFOX had fewer reports of diarrhea and better bowel function, while 5FUCRT resulted in lower rates of anxiety, nausea, and other symptoms; both treatments had distinct impacts on patients' health-related quality of life after surgery.
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Purpose: Lynch syndrome (LS)-associated colorectal cancer (CRC) is characterized by mismatch repair-deficiency (MMR-D) and/or microsatellite instability (MSI). However, with increasing utilization of germline testing, MMR-proficient (MMR-P) and/or microsatellite stable (MSS) CRC has also been observed. We sought to characterize MMR-P/MSS CRC among patients with LS.

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