Two-year Progression-free Survival Research Articles

Neoadjuvant chemotherapy followed by definitive local treatment in locally advanced sinonasal squamous cell carcinoma.

Sinonasal squamous cell carcinoma (SCC) is a rare disease entity, comprising less than 5% of malignancies of the head and neck. While surgery is the primary treatment approach, neoadjuvant and adjuvant therapies play crucial roles in enhancing the prognosis of patients undergoing treatment with the goal of cure. In this study, we aimed to explore the treatment outcomes of neoadjuvant chemotherapy (NAC) in patients with locally advanced sinonasal SCC. Medical records of patients diagnosed of locally advanced (cT3-4b, N0-3) sinonasal SCC treated with a definitive aim between January 2005 and March 2023 were retrospectively reviewed. Patients were categorized into the following groups based on the initial treatment: NAC followed by surgery, NAC followed by concurrent chemoradiotherapy (CCRT), definitive CCRT, or upfront surgery. Initial treatment plan was decided by a multidisciplinary team. Primary endpoint was overall survival (OS) and objective response rate, and secondary endpoints were progression free survival (PFS), cumulative incidence of local and distant failures, and treatment-related toxicity. The treatment response was assessed according to the RECIST criteria. Total 126 patients were included, and the median follow-up period was 25.6 months. The objective response rate to NAC was 48.2%. The subsequent resection rate was 70%, 42.9%, and 16.7% for patients with stage T3, T4a, and T4b disease, respectively. Two-year progression-free survival did not differ significantly between the NAC followed by surgery and upfront surgery groups (53.6% vs. 60.6%, P = 0.615) or between the NAC followed by CCRT and definitive CCRT groups (26.7% vs. 37.4%, P = 0.506). NAC may be a valuable treatment option for patients with locally advanced sinonasal SCC, as it provides an opportunity for curative surgery and exhibits non-inferior oncological outcomes compared with upfront definitive local treatments.

Comparison of R-CHOP-14 and R-mini-CHOP in older adults with diffuse large B-cell lymphoma-A retrospective multicenter cohort study.

Diffuse large B-cell lymphoma (DLBCL) is the most common lymphoma entity, and its incidence increases with age. There is a paucity of data regarding use of biweekly R-CHOP (R-CHOP-14) in patients ≥80 years of age. We performed a retrospective cohort study of patients with DLBCL aged ≥80 years treated with R-CHOP-14 and R-miniCHOP in two academic tertiary centers in Germany between 01/01/2005 and 12/30/2019. Overall, 79 patients were included. Median age was 84 years (range 80-91). Despite higher CR rates with R-CHOP-14 (71.4% vs. 52.4%), no statistically significant difference could be found between patients treated with R-CHOP-14 and R-miniCHOP regarding overall survival (OS) (p = .88, HR 0.94, 95% CI = 0.47-1.90) and progression-free survival (PFS) (p = .26, HR 0.66, 95% CI = 0.32-1.36). At a median follow-up of 40 months, the 2-year OS rates were 56% with R-CHOP-14 and 53% with R-miniCHOP. Two-year PFS rates were 46% for R-CHOP-14 and 50% for R-mini-CHOP. Relative dose intensity of chemotherapy did not correlate with OS (p = .72). With the caveat of a retrospective cohort study, we conclude that lacking a difference in OS, R-miniCHOP should be preferred for most patients with untreated DLBCL aged ≥80 years.

Predictive Factors for Early Immune Recovery in NHL Patients after Autologous Transplantation: A Multicenter Prospective Study.

Early lymphocyte recovery as manifested by an absolute lymphocyte count at d+15 (ALC-15) ≥ 0.5 × 109/L after autologous hematopoietic stem cell transplantation (AHCT) has been associated with a better outcome. This prospective multicenter study aimed to clarify factors associated with ALC-15 ≥ 0.5 × 109/L after AHCT among 178 patients with non-Hodgkin lymphoma. The mobilization capacity, as manifested by peak blood CD34+ cell numbers > 45 × 106/L correlated with higher ALC-15 levels (p = 0.020). In addition, the amount of CD3+CD4+ T cells > 31.8 × 106/kg in the infused graft predicted ALC-15 ≥ 0.5 × 109/L (p < 0.001). Also, the number of infused graft CD3+CD8+ T cells > 28.8 × 106/kg (p = 0.017) and NK cells > 4.4 × 106/kg was linked with higher ALC-15 (p < 0.001). The two-year progression-free survival after AHCT was significantly better in patients with ALC-15 ≥ 0.5 × 109/L (74 vs. 57%, p = 0.027). The five-year OS in patients with higher ALC-15 was 78% vs. 60% in those with lower ALC-15 (p = 0.136). To conclude, the mobilization capacity of CD34+ cells and detailed measures of graft cellular content mark prognostic tools that predict ALC-15 ≥ 0.5 × 109/L, which is associated with a better outcome in NHL patients after AHCT.

Lenalidomide and dexamethasone for Rosai-Dorfman disease: a single arm, single center, prospective phase 2 study

Rosai-Dorfman disease (RDD) is a rare heterogeneous histiocytic disorder lacking standardized first-line treatment. This single-center, phase 2 prospective study enrolled 13 newly diagnosed and 10 recurrent RDD patients from June 2021 to March 2023at Peking Union Medical College Hospital (Beijing, China). Lenalidomide 25mg days 1-21 plus dexamethasone 40mg days 1, 8, 15, 22 was administered in 28-day cycles, totaling 12 cycles. The primary endpoint was progression-free survival (PFS). Secondary endpoints were overall response rate (ORR) to lenalidomide and dexamethasone (RD) regimen, toxicity, and overall survival (OS) measured from RD start to death or last follow-up. OS and PFS were estimated according to Kaplan-Meier survival analysis and compared with the log-rank test. For OS and OR rate, 95% confidence limits were obtained using the Clopper-Pearson method, with standard methods used for PFS. p<0.05 was considered statistically significant. The trial was registered with ClinicalTrials.gov (NCT04924647). The median age was 44 years (IQR 35-54). All patients had extranodal RDD. MAPK pathway alterations occurred in 6/18 (33%). Elevated IL-6 and TNF-α were found in 39% (n=9) and 70% (n=16), respectively. All patients received ≥6 cycles (median 12, range 6-12, IQR 10-12). The ORR was 87% (20/23, 95% CI 66%-97%), 30% (n=7) complete remission, 57% (n=13) partial remission). Treatment with RD significantly decreased median serum levels of both IL-6 (from 5.9 (IQR 4.2-8.7) to 2.9 (IQR 2.1-5.9) pg/mL, p=0.031) and TNF-α (from 12.2 (IQR 8.6-17.9) to 8.3 (IQR 6.1-10.5) pg/mL, p=0.0012). With a median 26 months follow-up (range 6-28, IQR 16-28), 4 patients relapsed and none died. Two-year OS and PFS were 100.0% (95% CI 85%-100%) and 69.0% (95% CI 51%-94%), respectively. No grade 3-4 adverse events or discontinuations due to adverse events occurred. Twelve patients (n=12, 52%) had grade 1-2 hematological toxicity. Other toxicities included constipation (n=2, 9%), glucose intolerance (n=2, 9%), edema (n=2, 9%), insomnia (n=1, 4%), and tremor (n=1, 4%). Lenalidomide and dexamethasone regimen is an effective and safe regimen for newly diagnosed and recurrent RDD. National Natural Science Foundation of China, Beijing Natural Science Haidian frontier Foundation Funding, and the National High Level Hospital Clinical Research Funding.

Camrelizumab-based induction chemoimmunotherapy in locally advanced stage hypopharyngeal carcinoma: phase II clinical trial

This phase II trial aimed to determine the efficacy and safety of induction chemoimmunotherapy of camrelizumab plus modified TPF in locally advanced hypopharyngeal squamous cell carcinoma (LA HSCC) (NCT04156698). The primary endpoint was objective response rate (ORR), and secondary endpoints were 3-year overall survival (OS), progression-free survival (PFS), larynx preservation rate (LPR), and metastasis-free survival (MFS). Patients (cT3-4aN0-2M0), regardless of sex, received induction chemoimmunotherapy for three cycles: camrelizumab 200 mg d1, docetaxel 75 mg/m2 d1, cisplatin 25 mg/m2 d1-3, and capecitabine 800 mg/m2 bid d1-14, q21d. Patients were assigned to radioimmunotherapy if they had a complete or partial response, those with stable or progressive disease underwent surgery and adjuvant (chemo)radiotherapy. Camrelizumab was maintained post-radioimmunotherapy. Fifty-one patients were enrolled with a median follow-up duration of 23.7 months. After induction therapy, the ORR was 82.4% (42/51), meeting the prespecified endpoint. Grade 3/4 adverse events occurred in 26 patients, and no treatment-related death occurred. As three-year outcomes were immature, two-year OS, PFS and LPR were reported. As no distant metastatic event had occurred, MFS was not reported here. The two-year OS, PFS, and LPR rates were 83.0%, 77.1%, and 70.0%, respectively. The induction chemoimmunotherapy of camrelizumab plus TPF showed a high ORR rate with an acceptable safety profile in LA HSCC.

LGG-05. REPORT ON PEDIATRIC BRAIN TUMOR CONSORTIUM (PBTC)-029B, A PROSPECTIVE PHASE 2 CLINICAL TRIAL OF SELUMETINIB IN TREATING YOUNG PATIENTS WITH RECURRENT/PROGRESSIVE LOW-GRADE GLIOMA: NEW RESULTS ON STRATA 2, 5, AND 6 WITH UPDATED LONG-TERM SURVIVAL OUTCOMES ON STRATA 1, 3, AND 4

Abstract BACKGROUND PBTC-029B was a phase 2 trial evaluating efficacy of selumetinib (up to 26 courses) in children with recurrent/progressive low-grade glioma. We report new results on strata 2, 5, and 6 as well as update long-term survival outcomes on strata 1, 3, and 4. METHODS Stratum 2 enrolled children with pilocytic astrocytoma (PA) whose tumor screened negative for the BRAF-KIAA1549 fusion and the BRAFV600E mutation. Stratum 5 enrolled children with non-PA whose tumor screened positive for one of these two BRAF aberrations. Stratum 6 enrolled children who consented to tissue screening, but there was an assay failure. Responses were based on T2/FLAIR. RESULTS Stratum 2: among 14 patients, there was 1 partial response (PR), 7 stable disease (SD) and 6 progressive disease (PD) with overall response rate (ORR) of 7.1%. Two-year progression-free survival (PFS)/overall survival (OS) were 57.1/100%, respectively. Stratum 5: among 23 patients, there was 1 complete response, 4 PR, 12 SD and 6 PD with ORR of 21.7%. Two-year PFS/OS were 74.8%/100%, respectively. Stratum 6: among 26 patients, there were 7 PR, 14 SD and 5 PD with ORR of 26.9%. Two-year PFS/OS were 72.0%/100%, respectively. Long-term outcomes have now been evaluated in strata 1, 3, and 4. Stratum 1 enrolled patients with PA whose tumor screened positive for one of the two BRAF aberrations; stratum 3 enrolled patients with neurofibromatosis type-1 (NF1) associated pLGG; and stratum 4 enrolled non-NF1 optic pathway/hypothalamic tumors. Among strata 1, 3, and 4, the current median follow-up for patients without events are 60.4, 60.4, and 58.1 months, respectively. Five-year PFS/OS are 30.8%/88.9%, 54.2%/100%, and 51.0%/100%, respectively. CONCLUSIONS These data demonstrate that selumetinib provides tumor stability and responses among diverse pLGG tumors as well as show that many patients will achieve long-term disease control even several years after stopping treatment.

Neoadjuvant Nivolumab Plus Chemotherapy Followed By Response-Adaptive Therapy for HPV+ Oropharyngeal Cancer

Immune checkpoint inhibitors improve survival in recurrent and/or metastatic head and neck cancer, yet their role in curative human papillomavirus-positive oropharyngeal cancer (HPV+ OPC) remains undefined. Neoadjuvant nivolumab and chemotherapy followed by response-adaptive treatment in HPV+ OPC may increase efficacy while reducing toxicity. To determine the deep response rate and tolerability of the addition of neoadjuvant nivolumab to chemotherapy followed by response-adapted locoregional therapy (LRT) in patients with HPV+ OPC. This phase 2 nonrandomized controlled trial conducted at a single academic center enrolled 77 patients with locoregionally advanced HPV+ OPC from 2017 to 2020. Data analyses were performed from February 10, 2021, to January 9, 2023. Addition of nivolumab to neoadjuvant nab-paclitaxel and carboplatin (studied in the first OPTIMA trial) followed by response-adapted LRT in patients with HPV+ OPC stages III to IV. Primary outcome was deep response rate to neoadjuvant nivolumab plus chemotherapy, defined as the proportion of tumors with 50% or greater shrinkage per the Response Evaluation Criteria in Solid Tumors 1.1. Secondary outcomes were progression-free survival (PFS) and overall survival (OS). Swallowing function, quality of life, and tissue- and blood-based biomarkers, including programmed death-ligand 1 (PD-L1) expression and circulating tumor HPV-DNA (ctHPV-DNA), were also evaluated. The 73 eligible patients (median [range] age, 61 [37-82] years; 6 [8.2%] female; 67 [91.8%] male) started neoadjuvant nivolumab and chemotherapy. Deep responses were observed in 51 patients (70.8%; 95% CI, 0.59-0.81). Subsequent risk- and response-adaptive therapy was assigned as follows: group A, single-modality radiotherapy alone or transoral robotic surgery (28 patients); group B, intermediate-dose chemoradiotherapy of 45 to 50 Gray (34 patients); and group C, regular-dose chemoradiotherapy of 70 to 75 Gray (10 patients). Two-year PFS and OS were 90.0% (95% CI, 0.80-0.95) and 91.4% (95% CI, 0.82-0.96), respectively. By response-adapted group, 2-year PFS and OS for group A were 96.4% and 96.4%, and group B, 88.0% and 91.0%, respectively. Lower enteral feeding rates and changes in weight, as well as improved swallowing, were observed among patients who received response-adapted LRT. Pathologic complete response rate among patients who underwent transoral robotic surgery was 67.0%. PD-L1 expression was nonsignificantly higher for deeper responses and improved PFS, and ctHPV-DNA clearance was significantly associated with improved PFS. This phase 2 nonrandomized controlled trial found that neoadjuvant nivolumab and chemotherapy followed by response-adapted LRT is feasible and has favorable tolerability, excellent OS, and improved functional outcomes in HPV+ OPC, including among patients with high-risk disease. Moreover, addition of nivolumab may benefit high PD-L1 expressors, and sensitive dynamic biomarkers (eg, ctHPV-DNA) are useful for patient selection. ClinicalTrials.gov Identifier: NCT03107182.

Effects of immune-enhancing nutrition on radical cystectomy outcomes: Primary results from the randomized phase III double-blind clinical trial (S1600).

4501 Background: SWOG S1600 was a randomized, double-blind, phase III trial comparing the impact of consuming Specialized IMmunonutrition (SIM) to oral nutritional support (ONS) on postoperative complications following radical cystectomy (RC). SIM is fortified with nutrients: L-arginine; omega-3 fatty acids; and dietary nucleotides. Methods: Patients with bladder carcinoma planning to undergo RC were enrolled and randomized 1:1 to SIM vs. ONS. The primary endpoint was any (≥Grade I) postoperative complication assessed by the Clavien-Dindo (CD) scale at Day 30 after RC. Multivariable logistic regression was used, adjusted for the stratification factors: diversion type (neobladder vs. ileal conduit), prior neoadjuvant chemotherapy (any vs. none), and baseline nutrition status (well-nourished vs. moderate malnutrition). Additional outcomes included 90-day complications and high-grade (CD ≥Grade III) complications. Two-year progression-free survival (PFS) and overall survival (OS) were assessed; differences by arm were reported using Log-rank test statistics. Protocol-specified intention-to-treat (ITT) analyses based on all randomized patients and 1-sided alpha=.05 tests were performed. Results: Among N=203 enrolled patients (99 on SIM, 104 on ONS), median age was 68.8 years, 20% were female and 5% were Black. Five patients did not meet eligibility criteria (1 on SIM, 4 on ONS) but were included under the ITT design. Seventeen patients withdrew consent prior to their Day 30 assessment, and 8 patients were not assessed; thus, n=178 (90 on SIM, 88 on ONS) were evaluable at Day 30. The proportion of patients experiencing CD Grade ≥1 complications was 62.2% for SIM and 58.0% for ONS; in multivariable regression, there was no difference in Grade ≥1 complications by arm (OR=1.18, 95% CI, 0.64-2.18, 1-sided p=.71). There were no differences by arm in high-grade complications at Day 30, in any or high-grade complications at Day 90 or overall. To date, among all 203 patients, 17 on SIM and 26 on ONS have progressed or died, with 2-year PFS estimates of 77.2% and 68.3%, respectively (1-sided p=.16). Nine patients on SIM and 17 on ONS have died, with 2-year OS estimates of 87.4% and 78.2%, respectively (1-sided p=.07). Conclusions: There was no difference in any grade CD complications by type of nutritional supplement for patients with bladder cancer undergoing RC. Fewer patients on the SIM arm have progressed or died, although differences were not statistically significant; follow-up for survival will continue through 3-years after enrollment. Future work to understand the interaction of diet on cancers sensitive to immune modulation is needed. Clinical trial information: NCT03757949 .

A randomized phase II trial of 8 months of afatinib switching to osimertinib (A) versus osimertinib alone (B) as first-line treatment in advanced NSCLC patients with common EGFR mutation: YAMATO study (TORG1939/WJOG12919L).

8574 Background: NSCLC with common EGFR mutation (L858R or exon 19 deletion (Del19)) is known to originally comprise small portion of uncommon and compound EGFR variant cells including T790M-mutant ones albeit treatment-naïve. To overcome concomitant heterogeneous EGFR mutations, we planned a randomized phase II trial to assess the strategy of switching to osimertinib following 8 months of afatinib compared with osimertinib alone. Methods: YAMATO study is an open-label, multi-center, randomized phase II study. Patients with newly diagnosed stage III/IV/recurrent NSCLC harboring EGFR activating mutations (L858R or Del19) were randomized in a 1:1 ratio to receive up-front 8 months of afatinib (30 mg or 40 mg QD) followed by osimertinib (80 mg QD) (arm A) or osimertinib (80mg QD) alone (arm B) until disease progression or intolerable toxicity. The primary endpoint is 2-year progression free survival (PFS) rate with threshold rate of 22% and expected rate of 40% (one-tailed alpha of 0.1, beta of 0.2). Secondary endpoints are objective response rate (ORR), PFS, time to treatment failure, overall survival and adverse events. Results: Between May 2020 and Apr 2021, 113 patients were enrolled from 27 institutions (A/B 56/57). Patient characteristics were as follows: median ages, 73.5/71 years (range 41-85/41-92 years); proportion of males, 42.9/35.1%; EGFR mutation types, L858R/Del19 59/41% in A, 58/42% in B. The difference of two-year PFS rate was not observed statistically significant between groups (37.3% [80% CI, 29.0 to 45.5] in arm A vs 47.4% [80% CI, 38.5 to 55.7] in arm B; p=0.44; HR:1.28 [80% CI, 0.95-1.73]). The ORR was 82% in arm A and 87% in arm B. With the median follow-up of 27.5 months, median PFS was 16.8 months in arm A, and 22.2 months in arm B (HR: 1.280, p = 0.29). Severe pneumonitis occurred in 7% in arm A, most of which developed after switching to osimertinib, and 1.8% in arm B. Conclusions: YAMATO study failed to demonstrate the superiority of EGFR-TKI switching therapy of 8 months afatinib to osimertinib over osimertinib alone in terms of 2-year PFS rate in untreated advanced NSCLC patients with common EGFR mutations. Clinical trial information: 031200021 .

The incidence of and risk factors for radiation pneumonitis in patients treated with simultaneous bevacizumab and thoracic radiotherapy

BackgroundFirst-line chemotherapy combined with bevacizumab is one of the standard treatment modes for patients with advanced non-small cell lung cancer (NSCLC). Thoracic radiotherapy (TRT) can provide significant local control and survival benefits to patients during the treatment of advanced NSCLC. However, the safety of adding TRT has always been controversial, especially because of the occurrence of radiation pneumonia (RP) during bevacizumab treatment. Therefore, in this study, we used an expanded sample size to evaluate the incidence of RP when using bevacizumab in combination with TRT.Patients and methodsUsing an institutional query system, all medical records of patients with NSCLC who received TRT during first-line chemotherapy combined with bevacizumab from 2017 to 2020 at Shandong Cancer Hospital and Institute were reviewed. RP was diagnosed via computed tomography and was classified according to the RTOG toxicity scoring system. The risk factors for RP were identified using univariate and multivariate analyses. The Kaplan–Meier method was used to calculate progression-free survival (PFS) and overall survival (OS).ResultsUltimately, 119 patients were included. Thirty-eight (31.9%) patients developed Grade ≥ 2 RP, of whom 27 (68.1%) had Grade 2 RP and 11 (9.2%) had Grade 3 RP. No patients developed Grade 4 or 5 RP. The median time for RP occurrence was 2.7 months (range 1.2–5.4 months). In univariate analysis, male, age, KPS score, V20 > 16.9%, V5 > 33.6%, PTV (planning target volume)-dose > 57.2 Gy, and PTV-volume > 183.85 cm3 were correlated with the occurrence of RP. In multivariate analysis, male, V20 > 16.9%, and PTV-volume > 183.85 cm3 were identified as independent predictors of RP occurrence. The mPFS of all patients was 14.27 (95% CI, 13.1–16.1) months. The one-year and two-year PFS rates were 64.9% and 20.1%, respectively. The mOS of all patients was 37.09 (95% CI, 33.8–42.0) months. The one-year survival rate of all patients was 95%, and the two-year survival rate was 71.4%.ConclusionsThe incidence of Grade ≥ 2 RP in NSCLC patients who received both bevacizumab and TRT was 31.9%. Restricting factors such as V20 and PTV will help reduce the risk of RP in these patients. For patients who receive both bevacizumab and TRT, caution should be exercised when increasing TRT, and treatment strategies should be optimized to reduce the incidence of RP.

Treatment strategies and outcome in relapsed peripheral T-cell lymphoma: results from the Netherlands Cancer Registry

AbstractOptimal treatment in patients with refractory or relapsed peripheral T-cell lymphomas (R/R T-NHLs) is unknown. In this population-based study, outcomes in R/R peripheral T-cell lymphoma not otherwise specified (PTCL NOS), angioimmunoblastic T-cell lymphoma (AITL), and anaplastic lymphoma kinase-positive (ALK+) and ALK-negative (ALK–) anaplastic large cell lymphoma (ALCL) were evaluated. Patients with PTCL NOS, AITL, ALK+ ALCL, and ALK– ALCL (≥18 years) diagnosed in 2014 to 2019 were identified using the Netherlands Cancer Registry. End points were overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). The 2-year PFS of 821 patients was 57%. Among 311 patients with a relapse, 243 received second-line treatment: 44% received salvage chemotherapy, 20% received brentuximab vedotin (BV), and 36% received other treatment. In third-line treatment, BV was most commonly used (38%). ORR after second-line treatment was 47%. Two-year PFS and OS after relapse were 25% and 34%, respectively. The risk of second relapse was negatively affected by early relapse (<12 months after diagnosis), whereas BV reduced this risk compared with salvage chemotherapy. Reduced risk of relapse was independent of histological subtype. The best outcomes were observed for patients treated with salvage chemotherapy receiving consolidative autologous and allogeneic stem cell transplantation (SCT) (2-year OS 68%), patients treated with BV achieving a second complete remission (2-year OS 74%) and patients with allogeneic SCT (2-year OS 60%). The risk of second relapse was significantly lower for patients with R/R T-NHL treated with BV compared with patients treated with salvage chemotherapy, and this was irrespective of subtype. Therefore, the use of salvage chemotherapy for patients with R/R T-NHL is challenged.

Influence of the radiotherapy target volume and prognostic factors on the results of treatment of patients with cervical lymph nodes metastases of squamous cell carcinoma of unknown primary

Introduction: The issues of the radiotherapy target volumes in cases of cervical lymph nodes metastases of squamous cell carcinoma of unknown primary (SCCUP) remain unresolved due to the lack of clinical studies. Escalation or de-escalation of treatment may be directly related to prognostic factors. Purpose of this study was to evaluate the results of treatment using ipsilateral (only involved side of the neck) or total (bilaterally neck and pharyngeal mucosa) radiation therapy (RT) and to analyze the influence of clinical factors on overall survival (OS) and progression-free survival (PFS).Methods: A retrospective non-randomized clinical trial was conducted. Two-year OS and PFS were assessed in 26 SCCUP patients, who underwent combined treatment, including radiation therapy. Inoperable patients received either definitive RT (3.85 %) or sequential chemoradiation therapy (CRT, 11.5 %), or concurrent CRT (3.85 %). Operable patients underwent neoadjuvant RT with lymph node dissection (34.6 %) or lymph node dissection with adjuvant RT (11.5 %) or adjuvant sequential CRT (7.7 %) or adjuvant concurrent CRT (27 %); 50 % of patients received RT in a dose of more than 60 Gy, in 50 % it was less than 60 Gy. In 54 % of patients, only the ipsilateral cervical lymph nodes were included in the irradiation volume while 46 % of patients received RT to the pharyngeal mucosa and lymph nodes of the neck bilaterally (total radiation therapy group).Results: The median follow-up was 17 months. The 2‑year OS was 71.5 % (95 % CI 49.3–85.3 %), the 2‑year PFS was 72.1 % (95 % CI 44.5–87.6 %). There were no significant differences in 2‑year OS between the ipsilateral and total radiotherapy groups (HR = 1.08 [0.29–4.06], p = 0.904). Only a factor of extranodal extension (ENE) had a statistically significant impact on OS (HR = 6.05 [1.45–25.19], p = 0.0134).Conclusion: There was no statistically significant difference in 2‑year OS and PFS between the ipsilateral and total radiation therapy groups. A negative prognostic factor is the extranodal extension (ENE) of a metastatic tumor. Prospective randomized trials are needed.

Patterns and Incidence of Pneumonitis and Initial Treatment Outcomes with Durvalumab Consolidation Therapy after Radical Chemoradiotherapy for Stage III Non-Small Cell Lung Cancer.

Durvalumab consolidation after chemoradiotherapy for stage III non-small cell lung cancer (NSCLC) has become the standard of care. Single-center results were examined for treatment outcomes and patterns of pneumonitis in clinical practice. Patients with stage III NSCLC who underwent chemoradiotherapy at our institution (n = 150) were included. The patients were treated with chemoradiotherapy and durvalumab consolidation (Group D, n = 69) or chemoradiotherapy alone (Group N, n = 81). The overall survival (OS), progression-free survival (PFS), and the incidence of and risk factors for 12-month pneumonitis grade ≥ 2 (G2) were investigated. Two-year OS rates were 71.6% in Group D and 52.7% in Group N (p = 0.052). Two-year PFS rates were 43.0% in Group D and 26.5% in Group N (p = 0.010), although a propensity score matched analysis showed no significant difference. The incidence of 12-month pneumonitis ≥ G2 tended to be higher in Group D than in Group N (41.9% vs. 26.3%, p = 0.080). However, there was no difference in pneumonitis ≥ G3 rates (10.5% vs. 12.6%, p = 0.657). A multivariate analysis showed that the lung volume spared from 5 Gy (VS5) < 1800 cm3 was a risk factor for pneumonitis ≥ G2 in Group D. Durvalumab consolidation showed the potential to prolong PFS without increasing the severity of pneumonitis.

Neoadjuvant chemo-immunotherapy with camrelizumab plus nab-paclitaxel and cisplatin in resectable locally advanced squamous cell carcinoma of the head and neck: a pilot phase II trial

Neoadjuvant chemoimmunotherapy has emerged as a potential treatment option for resectable head and neck squamous cell carcinoma (HNSCC). In this single-arm phase II trial (NCT04826679), patients with resectable locally advanced HNSCC (T2‒T4, N0‒N3b, M0) received neoadjuvant chemoimmunotherapy with camrelizumab (200 mg), nab-paclitaxel (260 mg/m2), and cisplatin (60 mg/m2) intravenously on day one of each three-week cycle for three cycles. The primary endpoint was the objective response rate (ORR). Secondary endpoints included pathologic complete response (pCR), major pathologic response (MPR), two-year progression-free survival rate, two-year overall survival rate, and toxicities. Here, we report the perioperative outcomes; survival outcomes were not mature at the time of data analysis. Between April 19, 2021 and March 17, 2022, 48 patients were enrolled and received neoadjuvant therapy, 27 of whom proceeded to surgical resection and remaining 21 received non-surgical therapy. The ORR was 89.6% (95% CI: 80.9, 98.2) among 48 patients who completed neoadjuvant therapy. Of the 27 patients who underwent surgery, 17 (63.0%, 95% CI: 44.7, 81.2) achieved a MPR or pCR, with a pCR rate of 55.6% (95% CI: 36.8, 74.3). Treatment-related adverse events of grade 3 or 4 occurred in two patients. This study meets the primary endpoint showing potential efficacy of neoadjuvant camrelizumab plus nab-paclitaxel and cisplatin, with an acceptable safety profile, in patients with resectable locally advanced HNSCC.

Treatment regimens and survival among patients with head and neck squamous cell carcinoma from Mizo tribal population in northeast India – a single centre, retrospective cohort study

Patients with early-stage head and neck squamous cell carcinoma (HNSCC) are treated using a single-modality approach that involves either surgery (S) or radiotherapy (RT). Conversely, those with advanced-stage disease are treated using a multi-modality approach incorporating a combination of chemotherapy (CT), RT and S. In addition to behavioural factors, such as alcohol and tobacco use, clinical parameters, such as leukocyte and neutrophil counts and T and N classification, have been linked to the survival of patients with head and neck cancer. This retrospective study was designed to provide insights into the types of treatment (induction chemotherapy [IC], concurrent chemoradiotherapy [CCRT], S and RT) administered to patients with HNSCC in Mizoram, analyse their 2-year outcome, and identify potential factors that may affect the response to treatment. A retrospective cohort study was conducted using patients diagnosed with HNSCC between 2017 and 2020 in Mizoram, northeast India. Data on clinical and demographic factors and treatments provided were collected from medical records from the Mizoram State Cancer Institute, Mizoram. Overall survival (OS) and progression free survival (PFS) were determined for each factor using the Kaplan-Meier method and compared using the log-rank test. Cox regression analysis was used to identify the factors that affected OS and PFS. Multicollinearity test was performed between the predictors using a variance inflation factor cut-off point of2. A retrospective study was performed on 210 patients with HNSCC who were followed up for a period of 2 years. The findings revealed that hypopharynx was the most affected site, followed by the nasopharynx, oral cavity, oropharynx, and larynx. Regarding treatment regimens, 85/210 (40.5%) of the patients received IC along with CCRT or RT in a sequential manner. Moreover, 86/210 (41.0%) underwent CCRT alone, 22/210 (10.5%) received RT alone and 17/210 (8.1%) underwent surgery followed by adjuvant CCRT or RT. Two-year OS and PFS estimated using the Kaplan-Meier analysis were 78.1% (95% CI=72.4%-84.2%) and 57.4% (95% CI=50.8%-64.8%), respectively. Log-rank test showed that leucocytosis (p=0.015) and neutrophilia (p=0.014) exerted effects on OS, whereas nodal involvement (p=0.005), neutrophilia (p=0.043) and IC (p=0.010) exerted effects on PFS. Multivariate analysis indicated that leucocytosis (p=0.010 [OS], 0.025 [PFS]), neutrophilia (p=0.029, 0.033), cancer site (laryngeal) (p=0.009, 0.028) and nodal involvement (N2) (p=0.020, 0.001) were predictors of poor OS and PFS. OS was better than PFS in HNSCC patients from Mizo population. Multi-modality approach offered survival advantages over single-modality approach. Leucocytosis, neutrophilia, nodal involvement, and cancer sites were associated with poor OS and PFS. More comprehensive research with a larger sample size is needed to confirm the findings from this study. There is no funding for this study.

Retrospective assessment of neoadjuvant camrelizumab combined with induction chemotherapy: efficacy in laryngeal preservation for advanced hypopharyngeal and laryngeal squamous cell carcinoma

BackgroundHypopharyngeal and laryngeal squamous cell carcinoma (SCC) account for 25–30% of head and neck SCC. Total laryngectomy, while effective, compromises the quality of life. Immune checkpoint inhibitors such as Camrelizumab offer potential in laryngeal preservation. The study investigated Camrelizumab combined with TP regimen as a neoadjuvant therapy for laryngeal preservation in advanced hypopharyngeal and laryngeal SCC.MethodsA retrospective study was conducted at Sun Yat-sen University Cancer Center on patients diagnosed with locally advanced SCC of the hypopharynx and larynx from October 1, 2019, to October 25, 2022. The efficacy of a first-line treatment combining Camrelizumab (200 mg) and TP regimen (Albumin-bound paclitaxel at 260 mg/m2 and Cisplatin at 60 mg/m2) was evaluated using RECIST 1.1 criteria. Outcomes included overall survival (OS), progression-free survival (PFS), laryngectomy-free survival (LFS), and response rates.ResultsOf the 71 included patients, the median age was 60.7 years. Post the first-line treatment, 90.1% demonstrated an overall response. The one-year and two-year OS rates were 91.5% and 84.3%, respectively. One-year and two-year PFS rates were 92.9% and 83.9%, respectively, with LFS at 85.6% and 73.2%. The initial T4 stage as significantly associated with reduced OS and LFS. Skin reaction was the predominant adverse event.ConclusionThe Camrelizumab-TP regimen demonstrated promising results for advanced hypopharyngeal/laryngeal SCC patients, exhibiting high response rates, OS, and LFS, positioning it as a potential primary option for laryngeal preservation. Further comprehensive, randomized controlled studies are imperative to validate these initial observations and elucidate the regimen's full clinical efficacy in optimizing laryngeal outcomes.

Update from the PSMA-dRT trial: A randomized phase III trial of PSMA-PET prior to definitive radiation therapy for unfavorable intermediate-risk or high-risk prostate cancer.

291 Background: Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has superior diagnostic accuracy for detecting regional and distant metastases compared to conventional imaging (CT, bone scan, and MRI) in men with prostate cancer. This has the potential to guide definitive radiation therapy (dRT) patient selection and planning. Whether the use of improved diagnostic accuracy imaging improves patient outcomes remains to be demonstrated in clinical trials. Methods: This multi-institutional phase III randomized clinical trial (PSMA-dRT, NCT04457245) was designed to randomize 312 men with unfavorable intermediate-risk or high-risk prostate cancer 1.08:1 between receiving (n=162) and not receiving (n=150) a PSMA PET/CT prior to starting dRT. Treating radiation oncologists incorporated the PSMA PET/CT into radiotherapy planning. All other imaging modalities were allowed in the control arm. There were no prespecified androgen deprivation therapy (ADT) or dRT dose and volumes protocols. The primary endpoint was 5-year progression-free survival (PFS). Results: 54 patients were randomized between November 2020 and December 2021 (25 to PSMA PET/CT and 29 to control). The trial closed early following FDA approval and insurance coverage of PSMA PET/CT, since treatment without PSMA PET/CT in the control group was no longer acceptable for many patients and physicians. Among patients staged with PSMA PET/CT in the intervention group, 14 patients (58.3%) had localized miT2b-cN0M0 disease, 6 (25.0%) had locally advanced disease (miT3a-bN0M0), 3 (12.5%) had regional disease (miN1M0), and 1 (4.2%) had nodal and distant disease (miN1M1b). Four patients (16.7%) were upstaged relative to their staging at time of randomization. All three patients with miN1M0 disease received pelvic lymph node irradiation as part of their dRT course. The patient with miN1M1b disease received upfront ADT with abiraterone acetate and prednisone followed by consolidative radiotherapy to the prostate and pelvic lymph nodes. With a median follow-up of 21 months (interquartile range: 17.6-26.3 months), there were no cases of biochemical failure (PSA &gt;2 ng/mL above nadir), radiographic or biopsy-proven recurrence, salvage therapy, or prostate cancer death in either arm. Two-year PFS was 93.8% in the PSMA PET/CT arm (due to 2 non prostate cancer deaths) and 100% in the control arm. There was no significant difference in PFS between the PSMA PET/CT and control arms ( P=0.13). Conclusions: PSMA PET/CT upstaged 17% of patients compared to prior baseline staging, which allowed for more accurate treatment planning. Due to early termination, this trial was underpowered to assess the effect of PSMA PET/CT on PFS. PSMA-dRT is currently under submission for complete enrollment and data pooling at German sites. Clinical trial information: NCT04457245 .

Belantamab mafodotin, pomalidomide and dexamethasone in refractory multiple myeloma: a phase 1/2 trial

Due to evolving treatment standards for newly diagnosed multiple myeloma, many patients will be triple-class exposed after initial relapses and have poor survival. Novel therapies and combinations are therefore required to improve outcomes. B cell maturation antigen (BCMA)-targeted biologics have emerged as an important new area of therapeutics for relapsed multiple myeloma. The two-part ALGONQUIN trial evaluated various doses and schedules of the anti-BCMA antibody–drug conjugate belantamab mafodotin plus pomalidomide and dexamethasone for patients who are lenalidomide refractory and proteosome inhibitor exposed. The primary endpoints, including evaluating dose-limiting toxicities, establishing the recommended Part 2 dose (RP2D) and overall response rate for patients treated at the RP2D, were met. Secondary efficacy endpoints included progression-free survival and overall survival. Patients treated on study (N = 87) had a median of three previous regimens and 55.2% were triple-class refractory. At the RP2D the most common adverse events were decrease in best-corrected visual acuity (71.1%), keratopathy (65.8%), fatigue (57.9%), infection (47.4%; 7.9% grade ≥3), neutropenia (39.5%) and thrombocytopenia (39.5%). For RP2D patients (n = 38), the overall response rate was 85.3%, ≥very good partial response 75.7% and estimated two-year progression-free survival 52.8% (95% confidence interval, 33.9% to 82.4%), at a median follow-up of 13.9 months. The RP2D schedule was associated with manageable antibody–drug conjugate-associated corneal adverse events and improved tolerability without compromising efficacy. Belantamab mafodotin plus pomalidomide and dexamethasone induced durable responses with promising overall survival in relapsed multiple myeloma, the results of which are yet to be confirmed in the phase 3 DREAMM-8 study. ClinicalTrials.gov Identifier: NCT03715478.

Relevance of different prognostic scores in primary CNS lymphoma in the era of intensified treatment regimens: A retrospective, multicenter analysis of 174 patients.

Treatment intensification (including consolidative high-dose chemotherapy with autologous stem cell transplantation [HDT-ASCT]) significantly improved outcome in primary central nervous system lymphoma (PCNSL) patients. We conducted a multicenter, retrospective analysis of newly diagnosed PCNSL patients, treated with intensified treatment regimens. The following scores were evaluated in terms of overall survival (OS) and progression-free survival (PFS): Memorial Sloan-Kettering Cancer Center (MSKCC), International Extranodal Lymphoma Study Group (IELSG), and three-factor (3F) prognostic score. Further, all scores were comparatively investigated for model quality and concordance. Altogether, 174 PCNSL patients were included. One hundred and five patients (60.3%) underwent HDT-ASCT. Two-year OS and 2-year PFS for the entire population were 73.3% and 48.5%, respectively. The MSKCC (p = .003) and 3F score (p < .001), but not the IELSG score (p = .06), had the discriminatory power to identify different risk groups for OS. In regard to concordance, the 3F score (C-index [0.71]) outperformed both the MSKCC (C-index [0.64]) and IELSG (C-index [0.53]) score. Moreover, the superiority of the 3F score was shown for PFS, successfully stratifying patients in three risk groups, which also resulted in the highest C-index (0.66). The comparative analysis of established PCNSL risk scores affirm the clinical utility of the 3F score stratifying the widest prognostic spectrum among PCNSL patients treated with intensified treatment approaches.

Prediction of 5-year overall survival of diffuse large B-cell lymphoma on the pola-R-CHP regimen based on 2-year event-free survival and progression-free survival.

This study aimed to predict the 5-year overall survival (OS) benefit of pola-R-CHP versus R-CHOP in the POLARIX trial based on the 2-year event-free survival (EFS) and progression-free survival (PFS) rates in diffuse large B-cell lymphoma (DLBCL). We identified randomized controlled trials (RCT) published before 31 May 2023. The correlation between the logarithmic (log) hazard ratio (HR) for EFS (HREFS) or PFS (HRPFS) and the HR for OS (HROS) was estimated at the trial-level. Correlation analysis was performed between 2-year PFS or EFS and 5-year OS rates at the treatment arm-level. Linear regression models were used to calculate the 5-year OS of pola-R-CHP and R-CHOP. In the included 20 RCTs, a linear correlation between HREFS (r = 0.765) or HRPFS (r = 0.534) and HROS was observed at the trial- level. Two-year EFS (r = 0.918) or 2-year PFS (r = 0.865) correlated linearly with 5-year OS. Linear regression analysis between 2-year EFS/PFS and 5-year OS gave estimated 5-year OS rates between pola-R-CHP and R-CHOP of 6.4% and 6.3%, respectively. Two-year EFS and PFS are feasible early endpoints in patients with DLBCL treated primarily with immunochemotherapy. The pola-R-CHP regimen is expected to improve 5-year OS.