Faculty Bibliography

IMPORTANCE/OBJECTIVE:The rising incidence of HPV-positive oropharynx cancer (HPV-OPC) underscores the need for treatment strategies that maintain disease control while minimizing long-term toxicity. This study reports the long-term follow-up of de-escalation in poor prognosis HPV-OPC, providing critical data for future studies. OBJECTIVE:To evaluate long-term outcomes in patients with locally advanced HPV-OPC treated with induction chemotherapy (IC) followed by reduced-dose chemoradiation (rdCRT). We hypothesized that de-escalated radiation therapy after IC would be non-inferior to standard-dose CRT (sdCRT). DESIGN/METHODS:Two sequential clinical trials; Quarterback (QB) 1: phase III randomized control trial, QB 2: phase II non-randomized trial; patient accrual conducted between December 2012 and February 2022; final data cutoff April 2025. Median follow-up (IQR): 88.5 (64.6-118.2) months. SETTING/METHODS:Single-institution academic center. PARTICIPANTS/METHODS:62 patients with HPV-OPC were screened. 47 patients received rdCRT after IC and were included in the primary analysis. Key eligibility: smoking history ≤20 pack-years, no active smoking, no distant metastases, molecularly confirmed HPV status. INTERVENTIONS/METHODS:Three cycles of induction TPF (docetaxel, cisplatin, 5-fluorouracil) followed by rdCRT (5600 cGy) with weekly carboplatin in clinical responders; non-responders in both QB trials and responders in the control arm of QB1 received sdCRT (7000 cGy). MAIN OUTCOMES AND MEASURES/METHODS:Primary endpoints: 3-year locoregional relapse-free survival (LRRFS) and 3-year progression-free survival (PFS). Secondary: overall survival (OS). Tertiary: disease-specific survival. RESULTS:Among 47 patients treated with rdCRT after IC, the 3-year and 5-year LRRFS were 89.3% and 86.6%. PFS was 87.2% and 84.6% at 3 and 5 years. OS was 91.5% and 89.1% at 3 and 5 years. Six patients (13%) experienced locoregional failure, and two (4%) developed distant metastases. 7/8 treatment failures (87.5%) occurred in patients with extracapsular extension. CONCLUSIONS AND RELEVANCE/CONCLUSIONS:rdCRT following IC yields durable disease control in poor prognosis HPV-OPC, with outcomes comparable to historical benchmarks. Extended follow-up supports the safety and efficacy of this de-escalation strategy, even in patients with aggressive disease characteristics, but also underscores the need for careful patient selection, particularly in those with extracapsular extension.

BACKGROUND AND AIM/OBJECTIVE:Colonoscopy is the gold-standard screening test for colorectal cancer. However, it has come under scrutiny for its carbon footprint and contribution to greenhouse gas (GHG) emissions compared to other medical procedures. Notwithstanding, screening colonoscopies may have a positive effect on GHG emissions that is unknown. This study estimated the carbon emissions prevented by screening colonoscopies in the U.S. METHODS:Using the reported number of screening colonoscopies performed annually in the U.S. and the absolute risk reduction (ARR) reported in the NorDICC trial, we calculated the expected minimum number of cancer treatment and surveillance visits prevented through screening based on the cancer stage. The average carbon emission averted per mile traveled was computed using the Environmental Protection Agency's (EPA) GHG equivalencies calculator. The final estimate of carbon emissions averted over a decade by screening colonoscopies performed in one year was determined. RESULT/RESULTS:6.3 million screening colonoscopies performed in one year prevent 1,134,000 colorectal cancers over a ten-year period. Of these, 38∙3% (434,254) are localized, 38∙8% (440,281) are regional, and 22∙9% (259,465) are metastatic disease. The minimum number of post-diagnosis visits prevented is 11 for stage I, ≥ 21 for stage II, ≥25 for stage III, and ≥ 20 for stage IV disease, comprised of diagnostic, surgical evaluation, chemotherapy, and surveillance visits. The total number of visits prevented by screening is 2,388,397 for stage I, 5,254,421 for stage II, 13,120,369 for stage III, and 9,210,972 for stage IV disease. Approximately 395 million miles of travel and 158,263 metric tons of CO2, equivalent to 177 million pounds of coal burned, 19 billion smartphones charged, or 18 million gallons of gasoline consumed, were saved over ten years through screening. CONCLUSION/CONCLUSIONS:Colorectal cancer screening decreases cancer-related GHG emissions and minimizes the environmental impact of cancer treatment.

High-dose melphalan (HDM) followed by autologous hematopoietic cell transplantation (auto-HCT) remains the standard-of-care therapy for multiple myeloma (MM) even with the availability of proteasome inhibitors and immunomodulatory drugs. Gastrointestinal (GI) toxicity is the main cause of morbidity after HDM. Amifostine, a cytoprotective agent, may reduce HDM-associated GI toxicity. We conducted a case control study comparing HDM + auto-HCT with or without amifostine for MM patients. One hundred and seven patients treated at University Hospitals Cleveland Medical Center who received pre-transplant amifostine were compared to 114 patients treated at MD Anderson Cancer Center without use of this agent. Amifostine 740 mg/m² was administered as a bolus infusion at 24 h and 15 min before HDM. Patients' characteristics were similar in both the groups. Amifostine therapy was well tolerated without any significant adverse effects. Grade II or greater oral mucositis (27.1% vs 47.4%; p = .002), nausea (31.8% vs. 86.0%; p = .0001), vomiting (18.7% vs. 52.6%; p = .0001) and diarrhea (56.1% vs. 72.7%; p = .006) occurred less frequently in the amifostine-treated group. There was no discernable effect of amifostine on engraftment, progression-free or overall survival. Our results indicate that amifostine decreases GI toxicity while preserving anti-myeloma efficacy of HDM and auto-HCT.

OBJECTIVE: Despite an 80% response rate to chemotherapy, epithelial ovarian cancer has the highest case fatality rate of all gynecologic malignancies. Several studies have shown the efficiency of anticancer peptides PNC-27 and PNC-28 in killing a variety of cancer cells selectively in vitro and in vivo. The purpose of this study was to evaluate the efficacy of PNC-27 against human primary epithelial ovarian cancer. METHODS: We established primary cultures of freshly isolated epithelial ovarian cancer cells from patients with newly diagnosed ovarian cystadenocarcinomas. Two cell lines were obtained, one from mucinous cystadenocarcinoma, and the other from high-grade papillary serous carcinoma. The cancerous properties of these cells were characterized in vitro morphologically, by their growth requirements and serum independence. Treatment effects with PNC-27 were followed qualitatively by light microscopy, and quantitatively by measuring inhibition of cell growth using the MTT cell proliferation assay and direct cytotoxicity by measuring lactate dehydrogenase (LDH). RESULTS: PNC-27 inhibits in a dose-dependent manner the growth of and is cytotoxic to human primary cancer cells that had been freshly isolated from two ovarian epithelial cancers. The results further show that the control peptide PNC-29 has no effect on the primary cancer cells. Our results also show that PNC-27 is cytotoxic to cells from long-established and chemotherapy-resistant human ovarian cancer cell lines. CONCLUSION: These findings show, for the first time, the efficacy of PNC-27 on freshly isolated, primary human cancer cells. Our results indicate the potential of PNC-27 peptide as an efficient alternative treatment of previously untreated ovarian cancer as well as for ovarian cancers that have become resistant to present chemotherapies.