Impact of p16 Status on the Efficacy of Pembrolizumab Combined Nimotuzumab in Recurrent/Unresectable/Metastatic Head and Neck Squamous Cell Carcinoma Patients.

Decreased Frequency of MGMT Promoter Hypermethylation in Locally Relapsed Versus Locally Controlled p16 Negative Head and Neck Squamous Cell Carcinoma Patients after Chemoradiotherapy

BackgroundThe objective of our study was to investigate changes over the past decade in patient age and the prevalence of HPV in the population of patients with oropharyngeal carcinoma (OPC) treated at our center.MethodsWe performed a retrospective cohort study of patients treated at our cancer center for OPC between 2011 and 2021. Tissue biopsies were assessed for HPV status based on p16 staining for all patients.ResultsThere were 1,365 treated patients. The proportion of p16-positive patients increased from 43% in 2011 to 57.3% in 2021 (p = 0.01). The sex ratio was 3.6 M/1F for p16-positive and 3.7 M/1F for p16-negative patients (p = 0.94). The mean age increased from 60.2 y in 2011 to 63.6 y in 2021. The mean ages were 61.9 y for p16-positive and 61.7 y for p16-negative patients (p = 0.71), but there was a broader age distribution for the p16-positive patients (p = 0.03). The proportion of patients older than 70 y increased from 11% in 2011 to 28.2% in 2021, and this aging was similar between p16-positive (30.7% in 2021) and p16-negative (26.3% in 2021) patients. The 2-year and 5-year OS rates were 73.7% and 56.5% for the entire cohort. p16-positive patients had 2-year and 5-year OS rates of 86.8% and 77.4%, respectively, whereas p16-negative patients had 2-year and 5-year OS rates of 63.9% and 40.5%.ConclusionsAssessment of the change over the past decade in the population of patients with OPC at our center showed that HPV-positive OPC now appear to have overtaken HPV-negative cases in France, with 57.3% in 2021, and showed significant aging, with almost thirty percent of patients now older than 70 years. Those combined changes emphasize some of the challenges to be addressed in future OPC management.

Simple SummaryAnti-PD-1 immunotherapies are approved for head and neck squamous cell carcinoma in the recurrent/metastatic setting, and utilization of these high-cost biologics is expected to increase as other indications are approved. Due to the high cost and selective response rate of these immunotherapy biologics in HNSCC, it is imperative to better define which patient subsets will realize a clinically meaningful benefit with anti-PD-1 treatment. The impact of anatomical site and p16 status on the efficacy of anti-PD-1 inhibitors remains unresolved. We showed that anatomical site and p16 status are associated with overall survival in anti-PD-1-treated HNSCC patients from a single-institution, real-world cohort.In head and neck squamous cell carcinoma (HNSCC), anti-PD-1 inhibitors are approved for recurrent/metastatic (R/M) disease and anticipated to expand to other indications. The impact of p16 status and anatomical site on overall survival (OS) in immunotherapy-treated HNSCC patients remains unresolved. We performed a retrospective analysis of R/M HNSCC patients receiving anti-PD-1 immunotherapy at our academic medical center with an extensive community satellite network. Fifty-three R/M HNSCC patients were treated with anti-PD-1 immunotherapy and had a median OS of 6 months. Anatomical site was associated with distinct OS; oropharynx and larynx patients have superior OS compared to oral cavity patients. Analysis of the OPSCC subset showed p16+ status as a favorable, independent prognostic biomarker (HR 7.67 (1.23–47.8); p = 0.029). Further studies to assess the link between anatomical site, p16 status, and anti-PD-1 treatment outcomes in large cohorts of R/M HNSCC patients managed in real-world clinical practices and clinical trials should be prioritized.

Systemic ALK-Positive Anaplastic Large-Cell Lymphoma (ALCL): Final Analysis of an International, Individual Patient Data Study of 263 Adults

O-0013 Improved Early Prediction of Individual Prognosis for Patients with Metastatic Colorectal Cancer: Joint Modeling of Tumor Shrinkage with Volume Data

In this chapter we describe the experience gained using cisplatin and etoposide in childhood progressive low-grade glioma. After successfully adopting this combination in ten 3-day courses for progressive low-grade gliomas, the subsequent protocol, reducing the daily doses of cisplatin and etoposide, aimed at achieving the same response and 3-year PFS rates with lower neurotoxicity and myelotoxicity. In this second series we have treated 37 pts; 9 were metastatic cases. Treatment was prompted by radiological evidence of progression and/or clinical deterioration. A MRI volume reduction was appreciable in 65%; response was maximal 12 months after starting treatment. The 3-year EFS and OS rates were 65% and 97%, respectively for the whole series. Clinical, neurological or functional improvements were seen in 26/37 cases. Audiological toxicity caused alterations in 4/34 cases. The previous protocol had achieved volume reductions in 70% of cases, causing audiological damage (data updated) in 11/31 (p = 0.023), with 3-year PFS and OS rates of 70% and 100%, respectively. The updated 3-year PFS and OS rates were 85% and 96%, respectively, for those children treated in Milan. Lower doses of cisplatin/etoposide are still effective in progressive low-grade glioma, with less acute and persistent morbidity.KeywordsOverall SurvivalLipoic AcidPilocytic AstrocytomaSpine Magnetic Resonance ImagingIsolate Growth Hormone DeficiencyThese keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Objective To explore the long-term OS and recurrence-free survival (RFS) and the influencing factors in breast cancer patients. Methods According to the inclusion and exclusion criteria, a total of 2 423 breast cancer patients who underwent breast surgery in the Department of Breast Surgery, Fifth Medical Center, General Hospital of PLA from January 1, 2000 to December 31, 2015 were enrolled for a retrospective study. Kaplan-Meier method and log-rank test were used to compare the 5-year OS and RFS among patients with different clinical stages, molecular subtypes and surgical methods. Cox proportional hazard regression model was used to analyze the influencing factors on the patient survival. Results In 2 423 cases of breast cancer, the median age was 48 years, the median follow-up time was 5.2 years (range: 3.5-18.7 years) and the follow-up rate was 85.3%(2 066/2 423). The 5-year and 10-year OS rate was 91.5% and 84.4% respectively, and the 5-year and 10-year RFS rate (except stage Ⅳ breast cancer) was 85.8% and 78.4% respectively. As for clinical stage, the operable breast cancer accounted for 81.0% (1 963/2 423), local advanced breast cancer 15.6%(378/2 423)and stage Ⅳ breast cancer 3.4%(82/2 423). The 5-year OS rate in stage 0, Ⅰ, Ⅱ, Ⅲ and Ⅳ breast cancer was 100%, 98.5%, 93.8%, 78.1% and 50.8%, respectively, and the 5-year RFS rate (except stage Ⅳ breast cancer) was 98.5%, 95.4%, 87.0% and 63.0%, respectively. Clinical stage was significantly correlated with the 5-year OS and RFS rate of patients (χ2=356.067, 250.433, both P<0.001). As for molecular subtype, except 205 patients with unknown molecular type, the remaining 2 218 patients were divided into luminal, HER-2 overexpression and triple-negative subtypes according to the receptor status, accounting for 72.3%(1 604/2 218), 10.1%(225/2 218) and 17.5%(389/2 218), respectively. The 5-year OS rate of luminal, HER-2 overexpression and triple-negative subtypes was 93.1%, 88.3% and 84.4%, respectively, and the 5-year RFS rate (except stage Ⅳ breast cancer) were 87.7%, 84.8% and 76.7%, respectively. The 5-year OS and RFS rate presented a significant difference across three groups (χ2=24.124, 31.668, both P<0.001). As for surgical methods, the breast-conserving rate was 24.8% (600/2 423) in all patients. In stage Ⅰ breast cancer, the breast-conserving rate was 44.9%(309/688); the breast-conserving surgery group had a higher 5-year OS rate compared with mastectomy group (99.3% vs 98.4%, χ2=6.338, P=0.012); however the 5-year RFS rate showed no significant difference between two groups (96.7% vs 94.8%, χ2=2.245, P=0.134). In stage Ⅱ breast cancer, the breast-conserving rate was 21.1%(237/1 125), the 5-year OS rate in breast-conserving surgery group and mastectomy group was 97.2% and 92.7%, respectively and the 5-year RFS rate was 88.5% and 87.1%, respectively, indicating no significant difference between two groups (χ2=3.793, 1.425; P=0.051, 0.233). Cox proportional hazard regression analysis showed that age, clinical stage and molecular subtype were correlated with the OS of breast cancer patients (HR=1.017, 95%CI: 1.004-1.029, P=0.019; HR=3.242, 95%CI: 2.763-3.803, P<0.001, HR=1.203, 95%CI: 1.066-1.357, P=0.003). Conclusions Age, clinical stage and molecular subtypes are prognostic factors for breast cancer. In stage Ⅰ-Ⅱ breast cancer, the efficacy of breast-conserving surgery is superior to or not worse than mastectomy. Key words: Breast neoplasms; Survival rate; Neoplasm recurrence, local; Breast conserving surgery

Objective: To evaluate the expression of p-AKT and p-mTOR, the key proteins in PI3K/AKT/mTOR pathway in pediatric Burkitt lymphoma (BL), and to investigate the clinical and prognostic significance. Methods: Fifty-eight cases of pediatric BL and thirty cases of reactive hyperplastic lymphadenitis (RH) were collected at Children's Hospital of Fudan University from September 2011 to July 2018. Paraffin sections of tissues were immune stained for p-AKT and p-mTOR, and the expression was assessed and correlated with the clinical features and prognosis. Results: A total of 58 cases were diagnosed and 6 cases lost the follow-up. Of the remaining 52 BL patients including 43 males and 9 females, the median age was 5 years (range: 2 to 14 years). Regarding to the correlation between the two biomarkers, Spearman test showed that p-mTOR was positively associated with the expression of p-AKT (r=0.759, P<0.001). Of all BL patients, the positive rates of p-AKT and p-mTOR were 62.1% (36/58) and 60.3%(35/58) respectively, both significantly higher than control group (P=0.011, P=0.035 respectively). The presence of p-AKT was significantly associated with higher lactate dehydrogenase (LDH≥573 IU/L) level in patients of the disease (P=0.006), while p-mTOR was increased both in the higher LDH and lower ratio of albumin to globulin (A/G) group (P=0.006, P=0.034 respectively). Expression of p-AKT and p-mTOR did not show any statistical correlation with sex, age, St.jude stage, tumor size, B-symptom present or not, number of extra-nodal sites or international prognostic index (IPI) (P>0.05). Fifty-two patients had a median follow-up of 40 months (range: 5-87 months). Univariate analysis showed that p-AKT expression was significant in predicting both inferior OS (5-year estimate, 72.7% vs. 94.7%, χ(2)=4.123, P=0.042) and PFS (5-year estimate, 66.7% vs. 94.7%, χ(2)=5.822, P=0.016). The 5-year OS rate was 71.0% (22/31) for the p-mTOR positive cohort of patients compared to 95.2% (17/21) for p-mTOR negative group (χ(2)=4.881, P=0.027); however, there was no statistical significance in 5-year PFS rate (P>0.05). Especially, the 5-year OS and PFS rate of p-AKT/p-mTOR double-positive group were significantly lower than negative control group (including absence of single p-AKT or p-mTOR expression, and absence of both) (OS: 69.0% vs. 95.7%, χ(2)=6.285, P=0.012; PFS: 65.5% vs. 91.3%, χ(2)=5.405, P=0.020). The results of multivariate COX proportional risk regression analysis indicated that p-AKT/p-mTOR double-positive, higher LDH and IPI score 3-5 were independent prognostic factors for both OS and PFS, and the bulky tumor (>10 cm) for PFS of pediatric BL. Conclusion: The expression of p-AKT and p-mTOR may be a potential reference for diagnosis and the independent prognostic indicators of pediatric BL.

To evaluate the outcomes of refractory/relapsed cHL patients after high-dose chemotherapy (HDCT) and autologous stem cell transplantation (ASCT) in Beijing Cancer hospital and to identify the prognostic risk factors. We retrospectively analyzed 115 relapsed/refractory cHL patients who accepted HDCT and ASCT in our cancer center and had complete follow-up data from April 2000 to May 2017. Ages of these 115 patients at ASCT ranged from 14 to 63 (median age 28). Forty-four (38.3%) patients achieved CR and 50 (43.5%) patients achieved PR before ASCT. Thirty-seven (48.7%) patients of those 76 patients who did PET-CT before ASCT had negative PET-CT scans. The median follow-up time was 72 months. A total of 23 patients died in our study. The 5-year OS and PFS rates of all patients after ASCT were 78.7% and 53%, respectively. The 5-year OS rates after ASCT of patients who were in CR or PR or less than PR status before ASCT were 92.8%, 68.2%, and 76.2%, respectively (log-rank = 2.913, p = 0.233). And their 5-year PFS rates after ASCT were 69.2%, 54.2%, and 18.5%, respectively (log-rank = 13.615, p = 0.001). Univariate analysis revealed that ECOG (p = 0.010; hazard ratio = 1.578), disease status before ASCT (CR: p = 0.001; hazard ratio = 0.227) and after ASCT (CR: p < 0.001; hazard ratio = 0.154), and PET-CT results after ASCT (p = 0.023; hazard ratio = 0.438) significantly impact patients' PFS while number of pretransplant salvage chemotherapy (p = 0.037; hazard ratio = 2.521), radiotherapy (p = 0.046; hazard ratio = 0.423), and disease status after ASCT (CR: p = 0.010; hazard ratio = 0.197) significantly affected patients' OS. Multivariate analysis shown only disease status before ASCT (p = 0.002) had significant impact on PFS and disease status after ASCT (p = 0.021) had significant impact on OS. R/R HL patients can still obtain long-term PFS after HDCT and ASCT and disease status before ASCT was the most significant prognostic factor for PFS.

Relationship between p16 expression and prognosis in different anatomic subsites of OSCC.

Fractionated Busulfan, Fludarabine and Thiotepa Myeloablative Conditioning to Improve Transplant Outcomes for Myelofibrosis

ObjectiveThis study aimed to examine the correlation between smoking, alcohol drinking, and the prognosis of Nasopharyngeal Carcinoma (NPC). MethodsClinical data from 721 NPC cases treated at our hospital between January 2005 and December 2010 were collected. Information on smoking and drinking, including duration, daily quantity, and cumulative amount, was recorded and graded according to WHO standards. Statistical analysis was performed to assess the influence of smoking and alcohol drinking on NPC patient prognosis. After controlling for confounding factors, survival analysis compared the 5-year Progression-Free Survival rate (PFS) and Overall Survival rate (OS) among patients with varying degrees of smoking and drinking. The association between smoking, drinking, cumulative amount, and NPC patient prognosis was evaluated. Multivariate Cox regression analysis was then employed, considering patient demographic characteristics and clinical features, to comprehensively analyze prognostic influencing factors in NPC patients. Additionally, the multivariate Cox regression analysis was utilized to comprehensively examine the influencing factors of prognosis, taking into account the patients' basic demographic characteristics and clinical features. The findings revealed significant differences in the aforementioned rates. Results(1) Analysis of PFS and OS differences in NPC patients considered smoking status, smoking duration, daily smoking quantity, and cumulative smoking amount. No significant influence of smoking on NPC patient PFS and OS within 5-years was observed (p > 0.05). (2) Non-drinkers with NPC exhibited higher 5-year PFS and OS rates compared to drinkers (p = 0.047, p = 0.026). Furthermore, non-drinkers and those with a drinking duration of less than 120 months or between 120–240 months showed higher 5-year PFS and OS rates than individuals with a drinking duration exceeding 240 months (p < 0.05). Similarly, non-drinkers and individuals consuming less than 50 g/day had higher 5-year PFS and OS rates compared to those consuming 50–100 g/day or more than 100 g/day (p < 0.05). Additionally, the 5-year PFS and OS rates were higher in the non-drinking and light drinking groups compared to the moderate and heavy drinking groups (p < 0.05). (3) A partial synergistic effect between smoking and alcohol drinking was observed in NPC. (4) Alcohol drinking emerged as an independent prognostic factor for NPC. ConclusionAlcohol drinking is a significant factor influencing the prognosis of nasopharyngeal carcinoma, with the adverse effects further amplified when combined with smoking. Level of evidenceLevel 2.

Objective: To explore the therapeutic effects of transoral robotic surgery (TORS) and traditional surgical modes in oropharyngeal squamous cell carcinoma (OPSCC). Methods: The clinicopathological data of patients with oropharyngeal squamous cell carcinoma treated at Sun Yat-sen University Cancer Center from 2010 to 2018 were retrospectively analyzed. 135 cases were treated with traditional surgery (non-TORS group), while 52 cases were treated with TORS (TORS group). The prognosis of the two groups of patients were analyzed by Kaplan-Meier method and Log rank test, the influencing factors were analyzed by Cox regression model. Results: The 2-year overall survival (OS, 94.2%) and 2-year progression-free survival (PFS, 93.8%) of patients in the TORS group were better than those in the non-TORS group (71.4% and 71.4%, respectively, P<0.05). The 2-year OS (93.3%) and 2-year PFS (92.8%) of TORS group patients in T1-2 stage were better than those of non-TORS group (73.1% and 72.8%, respectively, P<0.05). The 2-year OS (95.8%) and 2-year PFS (95.2%) of patients with stage Ⅰ to Ⅱ in the TORS group were not significantly different from those in the non-TORS group (84.1% and 83.9%, respectively, P>0.05). The 2-year OS (92.9%) and 2-year PFS rate (92.7%) of patients with stage Ⅲ to Ⅳ in the TORS group were better than those in the non-TORS group (64.7% and 63.9%, respectively, P<0.05). The 2-year OS (94.4%) of HPV-positive patients in the TORS group was not significantly different from that in the non-TORS group (83.3%, P=0.222). The 2-year OS of HPV-negative patients in the TORS group (94.1%) was significantly different from that in the non-TORS group (43.7%, P<0.001). HPV status was an independent prognostic factor (P=0.008). Conclusions: TORS has a better prognosis in the treatment of oropharyngeal squamous cell carcinoma compared with the traditional treatment methods. The patients with T1-T2 can achieve better survival benefits after TORS treatment. The HPV-positive OPSCC patients has a better prognosis than that of HPV-negative OPSCC patients, and regardless of HPV status, OPSCC patients in the TORS group could obtain a better survival prognosis.

Diffuse large B-cell lymphoma (DLBCL) has been classified into different prognostic subgroups using immunohistochemistry in Western populations. However, the applicability in Chinese patients of these subgroups was unclear. We collected 116 specimens and performed immunohistochemical staining for CD10, BCL-6, MUM1, CD138, and CD5, and the results were classified into subgroups according to 3 different algorithms. We then analyzed the subgroups' correlation to patient survival. Expression of CD10 and BCL-6 predicted favorable 5-year OS (70 and 62.5%, respectively) and PFS (64.3 and 61.5%, respectively) rates. In contrast, the expression of MUM1 predicted unfavorable 5-year OS (23.1%) and PFS (17.9%) rates and was also independent of other markers. All algorithms led to useful subclassifications. Using Hans' algorithm based on CD10, BCL-6, and MUM1, the non-germinal center (GC) subgroup (66.4%) had worse 5-year OS (29.8%) and PFS (26.7%) rates than did the GC subgroup. Likewise, using Muris' algorithm based on CD10 and MUM1, fewer non-GC cases (27%) showed poorer OS (20.3%) and PFS (16.2%) rates than did GC cases, an effect that was independent of both the International Prognostic Index, a clinical indicator, and treatment. It identified a subgroup with a high-risk of death and seemed to be applicable in our series. In conclusion, these algorithms can be used effectively in Chinese patients with DLBCL.

Brentuximab Vedotin versus checkpoint inhibitors: Which one? When? Why should be preferred?