tbuckley/cabot-search huggingface dataset:
A phase II trial of neoadjuvant docetaxel/5-FU/cisplatin in combination with prophylactic pegteograstim in unresectable, locally advanced nasal cavity/paranasal squamous cell carcinoma: KCSG HN18-07.
Authors: Hojung An, Bhumsuk Keam, Seong Hoon Shin, Min Kyoung Kim, Sung-Bae Kim
Journal: Journal of Clinical Oncology (2024)

6020 Background: Squamous cell carcinoma (SCC) arising from paranasal sinus and nasal cavity (PNSNC) is often diagnosed at locally advanced stage. Neoadjuvant strategies have been explored to improve prognosis and facilitate organ preservation. The efficacy of triplet neoadjuvant chemotherapy (NAC) has not been established prospectively. We conducted a phase II trial of neoadjuvant docetaxel/5-FU/cisplatin (DFP) combined with prophylactic pegteograstim in unresectable, locally advanced PNSNC (KCT0003377). Methods: Eligible patients had unresectable SCC of PNSNC, were aged 19-75, had an ECOG performance status of 0/1, and demonstrated adequate organ function. Patients with distant metastasis were excluded. Criteria for unresectability included tumor or lymph node fixation, clinical T3/4 stage, or potential compromise of critical organ function (e.g., necessitating eyeball exenteration). NAC comprised three cycles of docetaxel (75mg/m2 on Day 1), cisplatin (75mg/m2 on Day 1, 60mg/m2 for those aged ≥65), and 5-FU (1,000mg/m2 on Days 1-4) administered every 3 weeks. Prophylactic pegteograstim (6mg) was administered on Day 6 or 7. The primary outcome was the overall response rate (ORR), with secondary outcomes including progression-free survival (PFS), the eyeball preservation rate at 24 months, and safety. The study required 28 patients to achieve a power of 80% (P0=0.45, P1=0.70, α-error=0.05, 10% dropout rate). Results: Between 2019 and 2023, 28 patients were screened, and 27 received at least one cycle of NAC. The median age was 58 years (range: 41-71), with 24 males. Seventeen had maxillary sinus origin, and ten had nasal cavity origin. Twenty-two patients had T4 disease, and six had N2 disease. The ORR was 64.3% (5 complete responses, 13 partial responses). Post-NAC treatments included surgery alone (n=2), concurrent chemoradiotherapy (CCRT) (n=15), surgery followed by CCRT (n=2), or radiotherapy (RT) (n=5). Procedures performed were total maxillectomy (n=4), partial maxillectomy (n=3), and endoscopic sinus surgery (n=2). With a median follow-up of 21.5 months (range: 0.1-53.0), the 2-year PFS and eyeball preservation rate were 64% and 100%, respectively. Fourteen patients experienced Grade ≥3 adverse events (AEs): hematologic (46.4%), non-hematologic (14.3%), with Grade 3/4 neutropenia (32.1%) and febrile neutropenia (14.3%). Dose reduction or delay occurred in 9 patients (33.3%). One patient died on Day 6 of cycle 1. Conclusions: DFP NAC demonstrated promising efficacy and an excellent eyeball preservation rate with manageable toxicity. DFP NAC with prophylactic pegteograstim, could be a reasonable option for patients with locally advanced SCC of the PNSNC. Follow-up is ongoing. Clinical trial information: KCT0003377 .
BMI correlation with outcomes in patients with head and neck cancer undergoing immunotherapy: A comprehensive review and meta-analysis.
Authors: Sakditad Saowapa, Chalothorn Wannaphut, Manasawee Tanariyakul, Phuuwadith Wattanachayakul, Pharit Siladech, Natchaya Polpichai, Lukman Aderoju Tijani
Journal: Journal of Clinical Oncology (2024)

6021 Background: Currently, the landscape of treating advanced malignancies has undergone a transformative shift with the advent of immunotherapy employing immune checkpoint inhibitors (ICIs). Notably, several ICIs have emerged as promising therapeutic modalities for individuals with head and neck cancer (HNC). An emerging body of evidence implies a plausible link between body mass index (BMI) and the effectiveness of ICIs in the broader context of cancer patients. Nevertheless, the specific correlation within the subset of head and neck cancer patients undergoing immunotherapeutic interventions remains unclear and warrants meticulous investigation. Methods: PubMed, Web of Science, and Google Scholar databases were searched extensively for records published until January 2024. Full-text articles aligned with the research objective were included, while records published in English, case reports, reviews, editorials, and studies reporting immunotherapy combined with other cancer therapies were excluded. The data required for review and analysis was abstracted in Excel files by two independent reviewers. Additionally, statistical analyses were performed using the Review Manager software, and methodological quality was assessed using the Newcastle Ottawa scale. Results: Only six studies were eligible for review and analysis. A subgroup analysis of data from these studies showed that obese HNC patients on immunotherapy had significantly better overall survival (OS) rates than non-obese patients (HR: 0.51; 95% CI: 0.29 – 0.93; p=0.03). However, the progression-free survival (PFS) was statistically similar between obese and non-obese patients (HR: 0.72; 95% CI: 0.39 – 1.33; p=0.30). In addition, when BMI was stratified as either low or high, no significant difference was observed in the OS and PFS of HNC patients (HR: 0.99; 95% CI: 0.59 – 1.66; p=0.97 and HR: 0.93; 95% CI: 0.61 – 1.41; p=0.42, respectively). Similarly, the statistical analyses showed that overweight patients have similar OS and PFS as patients with normal BMI (HR: 0.53; 95% CI: 0.15 – 1.92; p=0.33 and HR: 0.55; 95% CI: 0.20 – 1.52; p = 0.25, respectively). In contrast, underweight patients demonstrated poor OS and PFS (HR: 2.56; 95% CI: 1.29 – 5.12; p=0.008 and HR: 2.76; 95% CI: 1.17 – 6.52; p=0.02, respectively). Conclusions: Obese HNC patients on immunotherapy tend to have improved OS than non-obese patients, while underweight patients have worse clinical prognoses than those with normal or above BMI.
Impact of immune-related adverse events (irAE) onset on disease response and survival in patients (pts) with head-neck cancer treated with immune check point inhibitors (ICI).
Authors: Reema Patel, Omar Elghawy, Adam Barsouk, Varinder Kaur
Journal: Journal of Clinical Oncology (2024)

6028 Background: ICI or combination chemo-immunotherapy are the mainstay of therapy for metastatic head-neck squamous cell carcinoma (mHNSCC) due to durable responses in certain pts. irAEs have emerged as a new challenge in the management of these pts. Some studies suggest a positive correlation between irAE onset and ICI efficacy in other cancers, however, whether such an association exists in HNSCC remains incompletely explored. Methods: We performed a retrospective, single-center cohort study of pts ≥ 18 years of age, with histologically confirmed mHNSCC who received ≥ 1 dose of ICIs at the University of Virginia Comprehensive Cancer Center, VA, USA between 2013-2022. Demographics, disease and treatment characteristics, and clinical outcomes related to irAEs and ICI re-challenge were analyzed. IrAEs were graded using CTCAE v4.0 criteria by chart review. Independent sample t-tests and chi-square analyses were used for univariate comparisons. Median PFS and OS from ICI therapy initiation were estimated using Kaplan-Meier methodology and censored at date of last follow up. P-values &lt;0.05 were considered statistically significant. Results: Of 1979 pts who received ICI, 110 had mHNSCC (72.7% male; 84.5% White) with a median age of 62.4 years. ICI type included pembrolizumab or nivolumab in 109 pts, and nivolumab/ipilimumab in one pt. 53 (48%) pts experienced any grade irAE and 12 pts (11%) experienced &gt;1 irAE. The most common irAEs were hypothyroidism (30.4%), dermatitis (14.3%), and hepatitis (10.7%). CTCAE ≥G3 irAEs were seen in 22.6% pts (n=12). These included hepatitis (n=3), colitis (n=3), hypothyroidism (n=1), arthritis (n=1), pneumonitis (n=1), adrenal insufficiency (n=1), vasculitis (n=1), and cardiomyopathy (n=1). Men (62% vs 37%, p= 0.015) and pts with prior radiation therapy (83% vs 17%, p=0.047) were more likely to experience irAEs. Treatment interruption/discontinuation occurred in 43% pts with irAEs. Topical/supportive therapy was required in 52.8%, and 35.8% required systemic corticosteroids, with more than half experiencing complete irAE resolution. A statistically significant association was observed between irAE onset and objective response rate (68% vs 39%, p= 0.009). 12 pts underwent ICI re-challenge, resulting in partial response in 3 (25%), stable disease in 4 (33.3%) and progressive disease in 3 (25%) pts. There was no statistically significant difference in PFS (4.9 vs 9.7 months, p = 0.731) or OS (30.5 vs 21 months, p = 0.159) in irAE vs non-irAE groups, respectively. Conclusions: irAEs onset was associated with improved best response to ICI therapy in mHNSCC. Although OS was numerically superior in the irAE group, it did not meet statistical significance. ICI re-challenge is feasible in select pts, however further studies are needed to evaluate long term benefit of ICI re-challenge.
Efficacy of nimotuzumab added to concurrent chemoradiotherapy after induction chemotherapy for patients with locally advanced nasopharyngeal carcinoma.
Authors: Sangang Wu, Runjie Wang, Yifeng Yu, Ping Zhou, Chenlu Lian, Jun Wang, Qin Lin
Journal: Journal of Clinical Oncology (2024)

6024 Background: To investigate the efficacy and toxicities associated with adding nimotuzumab to concurrent chemoradiotherapy (CCRT) in locally advanced nasopharyngeal carcinoma (LANPC) patients who received induction chemotherapy (IC). Methods: Patients with stage III-IVA nasopharyngeal carcinoma who received IC (TPF/TP/GP) and platinum-based CCRT between January 2017 and October 2021 were retrospectively included. We performed propensity score matching (PSM) to balance and control confounding factors, and the matching variables included gender, age, T stage, N stage, and Epstein-Barr virus (EBV) status. Patients were divided into two treatment groups: CCRT+nimotuzumab (200mg iv, weekly for 7 courses) and CCRT alone. Primary endpoints were overall survival (OS) and disease-free survival (DFS), the secondary endpoints were locoregional recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS). Results: We screened 242 patients in the analysis. After PSM, 121 (50.0%) and 121 (50.0%) had CCRT+nimotuzumab and CCRT alone, respectively. The 3-year OS was 95.4% and 88.0% in those with and without nimotuzumab treatment (P=0.041), and the 3-year DFS of the CCRT+nimotuzumab group was significantly better than that in the CCRT alone group (90.3% vs. 77.5%, P=0.003). Similar LRFS was found between those with and without nimotuzumab treatment (96.5% vs. 93.7%, P=0.297). The 3-year DMFS for CCRT+nimotuzumab versus CCRT alone was 92.9% versus 82.5% (P=0.008). No significant differences in major toxicities were found between the two treatment arms including hematologic toxicities, hepatoxicity, nephrotoxicity, gastrointestinal reactions, and mucositis (P&gt;0.05). Conclusions: The addition of nimotuzumab to CCRT after IC in LANPC has shown promising results in treatment outcomes and acceptable toxicities.
Phase III randomized trial of intensity-modulated proton therapy (IMPT) versus intensity-modulated photon therapy (IMRT) for the treatment of head and neck oropharyngeal carcinoma (OPC).
Authors: Steven J. Frank, Paul Busse, David Ira Rosenthal, Mike Hernandez, David Michael Swanson, Adam S. Garden, Erich M. Sturgis, Renata Ferrarotto, Gary Brandon Gunn, Samir H Patel, NANCY Y. LEE, Alexander Lin, James W Snider, Mark William McDonald, Christina Henson, Gopal Krishna Bajaj, Noah Kalman, Upendra Parvathaneni, Sanford R. Katz, Robert Leonard Foote
Journal: Journal of Clinical Oncology (2024)

6006 Background: IMPT has unique biologic and physical properties compared with IMRT, limits radiation dose beyond the targeted tumor volumes, and is a novel de-intensification strategy for the management of head and neck tumors. This study was designed to compare the outcomes for patients with OPC after chemoradiation therapy (CRT) with IMRT vs IMPT. Methods: This is a multi-center, randomized, phase III non-inferiority OPC trial Stage III/IV (AJCC 7 th ) squamous cell carcinoma stratified patients by human papillomavirus status, smoking status, and receipt of induction chemotherapy (IC). The primary endpoint was the rate of progression-free survival (PFS) rate at 3 years, where progression was defined as disease recurrence or death. Under the null hypothesis, H0: r ≥ 1.535 established the margin for non-inferiority of IMPT. Secondary endpoints include overall survival (OS), treatment-related malnutrition, and gastrostomy-tube dependence. Analyses were conducted on intent-to-treat (ITT; n=440), per-protocol (PP; n=296), and as-treated (AT; n=397) populations. Results: Patients (n=440) were randomized to undergo IMRT(n=219) or IMPT (n=221) at 21 institutions. The median age was 61 years and HPV/p16 was positive in 95%. IC was the initial treatment in 13% of patients. All patients were treated with CRT to 70 Gy in 33 fx with bilateral neck treatment, and post-CRT surgical lymph node dissection occurred in 8%. The median follow-up was 3.14 years. In the ITT analysis, the hazard ratio (HR) for disease progression or death at 3 y was 0.87 (95%CI 0.56,1.35); p=0.006 and the corresponding HR for death (OS) was 0.63 (95%CI 0.36-1.10) suggesting a protective affect with IMPT. In PP analysis, the PFS HR was 0.85 (95%CI 0.52,1.38); p=0.009 and HR for death (OS) was 0.60 (95%CI 0.32-1.12). In the AT analysis, PFS HR was 0.88 (95%CI 0.56,1.37); p=0.007 and the corresponding HR for death (OS) was 0.70 (95%CI 0.40-1.22). For each analysis above, the null hypothesis was rejected and IMPT was non-inferior to IMRT. PP gastrostomy-tube dependence decreased with IMPT vs. IMRT from 42% to 28% (p=0.019), and more IMPT patients sustained their nutrition with end of treatment weight loss &lt; 5% from baseline: 24% vs 14% (p=0.037). Conclusions: IMPT is non-inferior to IMRT and has emerged as a standard of care CRT approach for OPC that reduces malnutrition and gastrostomy-tube dependence. Clinical trial information: NCT01893307 .
Long-term outcomes of anlotinib and penpulimab combined with chemotherapy in the treatment of patients with metastatic nasopharyngeal carcinoma that failed definitive platinum-based chemoradiotherapy.
Authors: Shuang Huang, Xiaozhong Chen, Song Qu, Shenhong Qu, Yaqian Han, Kunyu Yang
Journal: Journal of Clinical Oncology (2024)

6040 Background: The median progression-free survival (mPFS) of anti-PD-1 monoclonal antibody (mAb) plus gemcitabine (G) and cisplatin (C) in the first-line treatment of metastatic nasopharyngeal carcinoma (M NPC) is still limited in about 10 ~12 months. The tolerance is also unfavorable, especially for patients (pts) who had undergone platinum-based chemoradiotherapy (CRT) previously. We performed a phase 2 study to explore the potency of replacing cisplatin with anloinib (A), a multi-kinase inhibitor in combined with penpulimab (P), a novel anti-PD-1 mAb as the first-line treatment of M NPC for pts with prior explosure of platinum-based CRT. Here we report the updated long term outcomes of this study. Methods: This is a prospective, three cohorts, single-arm study. Eligible pts were aged 18 ~ 75 years old, diagnosed with NPC and developed metastasis after platinum-based CRT. Pts who were diagnosed as having M NPC at the first visit or experienced treatment failure within 6 months after definitive CRT or adjuvant therapy were excluded. Pts were randomized to receive G + A + P (cohort GAP), G + C + A + P (cohort GCAP) or G+C+P (cohort GCP). Gemcitabine (1000mg/m 2 , d1, d8) and cisplatin (80mg/m 2 , d1) were given intravenously for 4 to 6 cycles, 3 weeks per cycle. Penpulimab (200mg, d1) and anlotinib (10mg, qd, d1-14) were given intravenously and orally respectively until disease progression, or unacceptable toxicities. The primary endpoint was objective response rate (ORR). Results: 21 pts were randomized to three cohorts in lead-in phase while only cohort GAP was selected into expansion phase to enrolled another 7 pts. Finally, totally 28 pts were enrolled and received study treatment. The data cutoff date was December 1, 2023. The median follow-up was 20.2 month (95% CI: 17.0, 23.4). The results were summered in the table below. In cohort GAP, the confirmed ORR was 92.3% (95% CI: 64.0%, 99.8%) and the mPFS was still not reached (95% CI: NE, NE). The most common Grade 3 treatment-related adverse event (TRAE) was neutrophil count decreased (3 pts). Only one patient occurred Grade 4 TRAE (neutrophil count decreased) and no treatment-related death was observed. Conclusions: The long term outcomes of this phase 2 study preliminarily disclosed the advantage of the treatment regimen including gemcitabine, anlotinib and penpulimab as the first-line treatment of M NPC, especially for pts who had exposed to platinum-based chemotherapy. The further study with more sample size is warranted. Clinical trial information: NCT04736810 . [Table: see text]
Intra-treatment hypoxia directed major radiation de-escalation as definitive treatment for human papillomavirus-related oropharyngeal cancer.
Authors: NANCY Y. LEE, Eric Jeffrey Sherman, Heiko Schöder, Rick Wray, Charlie White, Lara Dunn, Tony Hung, David G. Pfister, Alan Loh Ho, Sean Matthew McBride, Yao Yu, Kaveh Zakeri, Noah Kalman, Charles Rutter, Luc Morris, Bhuvanesh Singh, Jay Boyle, Ian Ganly, Richard J. Wong, Nadeem Riaz
Journal: Journal of Clinical Oncology (2024)

6007 Background: We previously reported that surgery to the primary site with hypoxia-directed de-escalated radiation to the neck for human papillomavirus associated oropharyngeal carcinoma (HPV+ OPC) can lead to excellent oncologic outcomes. We now report the results of a successor multi-center phase II trial of hypoxia-directed de-escalated chemoradiotherapy without surgery for HPV+OPC. Methods: HPV+ OPC (T0-2/N1-N2c/AJCC 7 th ) patients were eligible for enrollment. Tumors without evidence of hypoxia on 18 F-FMISO (fluoromisonidazole) PET received de-escalated chemoradiation to 30Gy while those with hypoxia received chemoradiation to 70Gy. The primary objective was achieving a 2-year locoregional control (LRC) of 95% (failure was locoregional recurrence where surgical salvage was unfeasible) with a 7% non-inferiority margin. We enrolled a total of 158 subjects upfront to account for a 5% loss due to death (of reasons other than cancer) or follow-up. Secondary objectives were local failure (LF), regional failure (RF), distant metastasis (DM), overall survival (OS), toxicities, and patient-reported MD Anderson Dysphagia Inventory (MDADI) scores. LF, RF, and DM were estimated using the Cumulative Incidence Function, and OS was estimated using the Kaplan-Meier method. Results were reported up to 1/31/2024. Results: From 4/28/20-4/17/23, 158 HPV+ OPC patients were enrolled where150 patients were eligible for analyses. Patient characteristics: Tonsil (43%); Base of Tongue (47%); unknown primary (10%); &gt;/=10 pack years (22%); T0 (9%), T1 (44%), T2 (47%); N1 (14%), N2a (11%), N2b (59%), N2c (16%). 111 (74%) received 30Gy; 95% cisplatin. With 24 months (8-43) of median follow-up, the 2-year LF, RF, DM rates were 4.2%, 6.9%, 2.0%, respectively. The 2-year overall survival probability was 99%. Only 2 patients could not undergo salvage surgery [one 30Gy (second recurrence); one 70Gy (M1)], both received systemic therapy with durable response. Acute grade 3-4 toxicities were 32% (67% neutropenia). Mean MDADI scores: 92.93 (baseline); 68.24 (3 weeks), 91.45 (4 months) after chemoradiation. Conclusions: These early data indicate that major de-escalation to 30Gy based on hypoxia status achieved significant toxicity reduction without compromise in survival for HPV+ OPC treated with chemoradiation without surgery. Clinical trial information: NCT03323463 .
Endostar combined with concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone for locoregionally advanced nasopharyngeal carcinoma (LA-NPC): A phase III, prospective, randomised-controlled, multicenter clinical trial.
Authors: Min Kang, Daiyuan Ma, Jianquan Gao, Fen Wang, Bin Yu, Ying Lu, Yong Zhang, Fang Wu, Kai Hu, Tingting Zhang, Zhendong Yang, Lin Ruan, Yutao Qin, Zhuxin Wei, Zhen Meng, Huan Dong, Yating Qin, Ziyan Zhou, Yuanxiu Yin, Rensheng Wang
Journal: Journal of Clinical Oncology (2024)

6002 Background: Cisplatin-based concurrent chemoradiotherapy (CCRT) has long been regarded as standard treatment for LA-NPC. However, approximately 30% of patients still fail to obtain a satisfactory effect. Endostar (Rh-endostatin), an anti-angiogenesis inhibitor, is well-tolerated and has been reported as a promising complement to CCRT. This trial aimed to evaluate the efficacy and safety of adding Endostar to CCRT for LA-NPC. Methods: In this prospective, randomized phase III study, patients with LA-NPC (stage III-IVb, 7 th edition) were enrolled at 6 centers in China, and randomly assigned (1:1) to receive Endostar plus CCRT (CCRT+E group, n=150) or CCRT alone (CCRT group, n=150). Endostar (7.5 mg/m2/day, days 1-10, 15 days/cycle) was given continuously intravenously for 5 cycles (3 concurrent from 5 days before radiotherapy, and 2 adjuvant from the first day after the completion of radiotherapy). The primary endpoint was the progress-free survival (PFS) rate. The secondary endpoints included overall survival (OS), distant metastasis-free survival (DMFS), local-regional relapse-free survival (LRRFS), the rate of complete response (CR) at 3 months after RT, and safety. Results: Between November 2016 and July 2020, 300 patients with LA-NPC were randomized (CCRT+E group, 150; CCRT group, 150). As of the data cutoff (December 2023), the median follow-up was 66 months. Intention-to-treat analysis showed that patients in the CCRT+E group achieved better CR rate at 3 months after RT (90.0% vs 80.7%, P=0.022). The 3-year PFS was 84.8% in the CCRT+E group, and 75.1% in the CCRT group (HR, 0.544; 95% CI, 0.336-0.879; P log-rank =0.011). The 3-year OS was 89.2% vs. 85.3% (HR, 0.595; 95% CI, 0.361-0.982; P log-rank =0.039). The 3-year DMFS was 89.7% vs. 80.5% (HR, 0.468; 95% CI, 0.266-0.821; P log-rank =0.007). The 3-year LRRFS was 91.5% vs. 90.8% (HR, 0.808; 95% CI, 0.407-1.604; P log-rank =0.541). Patients in the CCRT+E group and in the CCRT group had similar Grade 3-4 acute and late toxicity profile (61.7% vs. 65.3%, p=0.519 and 8.0% vs.7.3%, p=0.815). Conclusions: The addition of Endostar to standard CCRT significantly improved the 3-year PFS of LA-NPC patients with good safety profile. Clinical trial information: NCT02907710 .