Induction Chemotherapy Response Research Articles

The role of induction chemotherapy for orbital invasion in sinonasal malignancies: A systematic review.

Sinonasal malignancies (SNMs) frequently present with orbital invasion. Orbital exenteration (OE) can lead to significant morbidity. Induction chemotherapy (IC) is a promising treatment alternative that may allow for orbit preserving (OP) treatments without compromising patient survival. This systematic review was conducted to synthesize the published data on SNM patients with orbital invasion who underwent IC, including tumor response, orbital outcomes, and survival. The study protocol was designed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Databases Embase, Cochrane, Medline, and Scopus, from inception to July 17, 2023, were searched. Nineteen studies were included, encompassing 305 SNM patients with orbital invasion treated with IC. Fourteen studies reported an overall IC response rate (positive response defined as complete or partial tumor volume reduction) of 77.2%. Among included studies, OE rates after IC ranged from 0 to 40%. Three studies reported a high rate of posttreatment functional orbital preservation (89.8-96.0%). Five studies specifically reported that 62.5% (60 out of 96) of patients were downgraded from planned OE to OP treatment following IC. Three studies reported a significant overall survival (OS) improvement in IC responders versus IC nonresponders. Following IC, 5-year OS ranged from 44.2 to 55.5%. Patients with olfactory neuroblastoma demonstrated the highest IC response rate and lowest OE rate (100 and 0%, respectively) versus those with sinonasal undifferentiated carcinomas (68.4 and 0%) or squamous cell carcinomas (76.7 and 16%). For select patients, IC may allow for OP in locally advanced SNMs with orbital involvement.

Efficacy and safety of induction chemotherapy in oral cavity cancer: An eight-year experience at a Portuguese reference center.

Induction chemotherapy has been described as an option in locally advanced oral cavity squamous cell carcinoma when the surgical morbidity is expected to be high. This work aimed to evaluate the outcome and safety of induction chemotherapy in this setting. We performed a retrospective and observational study including patients with oral cavity squamous cell carcinoma, treated with induction chemotherapy between January 2010 and December 2018. Outcomes included induction chemotherapy toxicity, treatment response, disease-free survival and overall survival. A total of 108 oral cavity squamous cell carcinoma patients were included. Ninety-six (88.9%) had stage IV disease, while 12 (11.1%) had stage III. Eighty-four patients (80.8%) achieved at least a partial response to induction chemotherapy at clinical evaluation, and 75 (72.1%) at radiological evaluation. Seventy-eight patients have been proposed for subsequent definitive treatments, with no differences obtained in prognosis, when comparing surgical to non-surgical approaches. In patients treated with definitive treatments, improved five-year disease-free survival was obtained if at least a clinical (56.3%; p=0.001) or radiological (52.9%; p=0.001) partial response was achieved after induction chemotherapy. Similarly, superior five-year overall survival was verified for those achieving at least clinical (51.1%; p<0.0001) or radiological (52.6%; p=0.001) partial response. Also, accomplishing a pathologic complete response (n=22.6%) significantly improved disease-free survival (p=0.039) and overall survival (p=0.005). Grade 3 and 4 toxicities were observed in 52 patients (41.8%). Responses to induction chemotherapy predicted prognosis in our population, however important toxicities were observed. Further studies are necessary to identify induction chemotherapy response predictors and subgroups who may benefit from this approach.

Comparison of response and toxicity of induction chemotherapy with cisplatin and 5-fluorouracil versus cisplatin and paclitaxel followed by concurrent chemoradiotherapy in advanced head and neck cancer

Background: Head and neck cancer poses a prevalent oncological challenge in Bangladesh, often diagnosed in advanced stages. Standard treatment for inoperable cases involves concurrent chemo-radiotherapy, but induction chemotherapy has shown significant benefits. This study aimed to compare the response and toxicity of induction chemotherapy with cisplatin and 5-fluorouracil versus cisplatin and paclitaxel followed by concurrent chemo-radiotherapy in advanced head and neck cancer. Methods: From January 2019 to June 2020, a multicenter study enrolled 150 cases with inoperable squamous cell carcinomas in the head and neck. Ethical approval was obtained from Bangabandhu Sheikh Mujib Medical University. Divided into two arms, Arm A had 75 patients receiving cisplatin and 5-fluorouracil, while Arm B had 75 patients receiving cisplatin and paclitaxel for three cycles. Results: After 24 weeks of treatment, complete response rates were 53.33% in Arm A and 56.0% in Arm B, with partial response rates of 29.33% and 32.0% respectively. Overall response was 82.66% in Arm A and 88.0% in Arm B, showing no statistically significant difference (p&gt;0.05). Arm A exhibited more anemia, oral mucositis, skin toxicity, and hand- foot syndrome, while Arm B had higher neuropathy. Hematological and non-hematologic toxicities during concurrent chemo-radiotherapy were similar in both arms. Conclusions: Induction chemotherapy with cisplatin and paclitaxel, followed by concurrent chemo-radiotherapy, is equally effective as induction chemotherapy with cisplatin and 5-fluorouracil, followed by concurrent chemo-radiotherapy, in treating advanced head and neck squamous cell carcinoma. However, the former regimen demonstrates significantly fewer toxicities, indicating a safer treatment option.

Higher TIGIT+ γδ TCM cells may predict poor prognosis in younger adult patients with non-acute promyelocytic AML.

γδ T cells recognize and exert cytotoxicity against tumor cells. They are also considered potential immune cells for immunotherapy. Our previous study revealed that the altered expression of immune checkpoint T-cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) on γδ T cells may result in immunosuppression and is possibly associated with a poor overall survival in acute myeloid leukemia (AML). However, whether γδ T-cell memory subsets are predominantly involved and whether they have a relationship with clinical outcomes in patients with AML under the age of 65 remain unclear. In this study, we developed a multicolor flow cytometry-based assay to monitor the frequency and distribution of γδ T-cell subsets, including central memory γδ T cells (TCM γδ), effector memory γδ T cells (TEM γδ), and TEM expressing CD45RA (TEMRA γδ), in peripheral blood from 30 young (≤65 years old) patients with newly diagnosed non-acute promyelocytic leukemia (also known as M3) AML (AMLy-DN), 14 young patients with AML in complete remission (AMLy-CR), and 30 healthy individuals (HIs). Compared with HIs, patients with AMLy-DN exhibited a significantly higher differentiation of γδ T cells, which was characterized by decreased TCM γδ cells and increased TEMRA γδ cells. A generally higher TIGIT expression was observed in γδ T cells and relative subsets in patients with AMLy-DN, which was partially recovered in patients with AMLy-CR. Furthermore, 17 paired bone marrow from patients with AMLy-DN contained higher percentages of γδ and TIGIT+ γδ T cells and a lower percentage of TCM γδ T cells. Multivariate logistic regression analyses revealed the association of high percentage of TIGIT+ TCM γδ T cells with an increased risk of poor induction chemotherapy response. In this study, we investigated the distribution of γδ T cells and their memory subsets in patients with non-M3 AML and suggested TIGIT+ TCM γδ T cells as potential predictive markers of induction chemotherapy response.

Gene polymorphisms of molecules of the cGAS-STING signalling pathway are associated with AML in Chinese patients

PurposeThe aim of this study was to explore the relationships between single-nucleotide polymorphisms (SNPs) of crucial molecules in the cGAS-STING signalling pathway and the susceptibility to, induction chemotherapy response of, and prognosis of acute myeloid leukaemia (AML) in Chinese patients.MethodsThirteen SNPs of crucial molecules in the cGAS-STING signalling pathway were genotyped in 262 AML patients using the Sequenom MassARRAY system. The associations of SNPs with susceptibility, and induction chemotherapy response were analysed using the chi-square test or Fisher’s exact test and univariate binary logistic regression, the connection of SNPs with prognosis of AML was analysed using the log-rank test, and Kaplan–Meier curves were applied for survival estimation.ResultsIn our study, gene polymorphisms of cGAS-STING signalling pathway molecules could be vitally associated with AML. In the recessive model, the cGAS rs311678 gene polymorphism could be closely related to AML susceptibility (CC vs. TT + TC, odds ratio (OR) = 0.480, 95% confidence interval (CI) = 0.260–0.889, p = 0.020). Moreover, IKKA rs3808917 might be associated with the WBC count, cGAS rs311678 could be associated with the bone marrow (BM) blast percentage, and NF-κB rs1056890 under codominant and recessive models could be connected with the HGB level. Patients who were STING rs7380272 TT/CT carriers was likely to have higher insensitivity to induction chemotherapy than CC carriers (TT + CT vs. CC, OR = 2.917, 95% CI = 1.073–7.929, p = 0.036). Survival analysis indicated that the IKKB rs3747811 TT genotype might be associated with decreased overall survival (OS) (p < 0.05).ConclusionsSNPs of molecules in the cGAS-STING signalling pathway could be significantly associated with AML. The cGAS rs311678 gene polymorphism could be associated with AML susceptibility, the STING rs7380272 variant might be related to induction chemotherapy response, and IKKB rs3747811 tended to be associated with AML overall survival. Moreover, IKKA rs3808917 could be associated with the WBC count, cGAS rs311678 could be associated with the BM blast percentage, and NF-κB rs1056890 might be related to the HGB level.

Response Of Bortezomib, Cyclophosphamide And Dexamethasone Induction Chemotherapy In Multiple Myeloma Patients Presenting To Combined Military Hospital Rawalpindi

Objective: To determine the response rate and tolerability of Bortezomib, Cyclophosphamide and Dexamethasone (VCD) induction therapy in multiple myeloma patients. Study Design: Prospective longitudinal study Place and Duration of Study: Department of Oncology, Combined Military Hospital, Rawalpindi Pakistan, from Mar to Sep 2020. Methodology: Patients of either gender aged &gt;20-65 years, newly diagnosed cases of multiple myeloma, Durie-Salmon stage II/III, were included. Patients were given Bortezomib, Cyclophosphamide and Dexamethasone induction therapy for a 21-day cycle. Response rate and tolerability were measured. Results: A total of 147 patients were included in the study. There were 75(51%) male and 72(49%) female.The overall response rate was seen in 93(63.3%) patients, complete response was seen in 30(20.4%), and partial response was seen in 63(42.9%) patients. The overall response rate was significantly associated with age, myeloma type, and Karnofsky's performance status (p-value&lt;0.001). Conclusion: The novel sequential 3-drug combination of Bortezomib, Cyclophosphamide and Dexamethasone is safe and well tolerated for multiple myeloma patients. The results of the current study increase evidence of a moderately high response rate with Bortezomib, Cyclophosphamide and Dexamethasone induction therapy.

Utility of contrast-enhanced MRI radiomics features combined with clinical indicators for predicting induction chemotherapy response in primary central nervous system lymphoma.

To assess the utility of combining contrast-enhanced magnetic resonance imaging (CE-MRI) radiomics features with clinical variables in predicting the response to induction chemotherapy (IC) for primary central nervous system lymphoma (PCNSL). A total of 131 patients with PCNSL (101 in the training set and 30 in the testing set) who had undergone contrast-enhanced MRI scans were retrospectively analyzed. Pyradiomics was utilized to extract radiomics features, and the clinical variables of the patients were gathered. Radiomics prediction models were developed using different combinations of feature selection methods and machine learning models, and the best combination was ultimately chosen. We screened clinical variables associated with treatment outcomes and developed clinical prediction models. The predictive performance of radiomics model, clinical model, and combined model, which integrates the best radiomics model and clinical characteristics, was independently assessed and compared using Receiver Operating Characteristic (ROC) curves. In total, we extracted 1598 features. The best radiomics model we selected as the best utilized T-test and Recursive Feature Elimination (RFE) for feature selection and logistic regression for model building. Serum Interleukin 2 Receptor (IL-2R) and Eastern Cooperative Oncology Group (ECOG) Score were utilized to develop a clinical predictive model for assessing the response to induction chemotherapy. The results of the testing set revealed that the combined prediction model (radiomics and IL-2R) achieved the highest area under the ROC curve at 0.868 (0.683, 0.967), followed by the radiomics model at 0.857 (0.681, 0.957), and the clinical prediction model (IL-2R and ECOG) at 0.618 (0.413, 0.797). The combined model was significantly more accurate than the clinical model, with an AUC of 0.868 compared to 0.618 (P < 0.05). While the radiomics model had slightly better predictive power than the clinical model, this difference was not statistically significant (AUC, 0.857 vs. 0.618, P > 0.05). Our prediction model, which combines radiomics signatures from CE-MRI with serum IL-2R, can effectively stratify patients with PCNSL before high-dose methotrexate (HD-MTX) -based chemotherapy.

Embracing Personalized Strategies in Radiotherapy for Nasopharyngeal Carcinoma: Beyond the Conventional Bounds of Fields and Borders.

Radiotherapy is the primary treatment modality for non-metastatic nasopharyngeal carcinoma (NPC) across all TN-stages. Locoregional control rates have been impressive even from the 2D radiotherapy (RT) era, except when the ability to deliver optimal dose coverage to the tumor is compromised. However, short- and long-term complications following head and neck RT are potentially debilitating, and thus, there has been much research investigating technological advances in RT delivery over the past decades, with the primary goal of limiting normal tissue damage. On this note, with a plateau in gains of therapeutic ratio by modern RT techniques, future advances have to be focused on individualization of RT, both in terms of dose prescription and the delineation of target volumes. In this review, we analyzed the guidelines and evidence related to contouring methods, and dose prescription for early and locoregionally advanced (LA-) NPC. Next, with the preference for induction chemotherapy (IC) in patients with LA-NPC, we assessed the evidence concerning radiotherapy adaptations guided by IC response, as well as functional imaging and contour changes during treatment. Finally, we discussed on RT individualization that is guided by EBV DNA assessment, and its importance in the era of combinatorial immune checkpoint blockade therapy with RT.

Effect of single-nucleotide polymorphism in SLCO1B1 and CDA genes on response and toxicity of induction chemotherapy in acute myeloid leukemia

Effect of single-nucleotide polymorphism in SLCO1B1 and CDA genes on response and toxicity of induction chemotherapy in acute myeloid leukemia

Machine Learning-Based MRI Radiogenomics for Evaluation of Response to Induction Chemotherapy in Head and Neck Squamous Cell Carcinoma

To develop and validate a radiogenomics model integrating clinical data, radiomics-based machine learning (RBML) classifiers, and transcriptomics data for predicting the response to induction chemotherapy (IC) in patients with head and neck squamous cell carcinoma (HNSCC). Radiomics features derived from T2-weighted, pre- and post-contrast-enhanced T1-weighted MRI sequences, clinical data, and RNA sequencing data of 150 patients with HNSCC were included in the study. Analysis of variance or recursive feature elimination was used to reduce radiomics features. Three RBML classifiers were developed to distinguish non-responders from responders. Weighted correlation network analysis (WGCNA) was performed to identify the correlation between clinical data or radiomics features and molecular features; subsequently, protein interaction and functional enrichment analyses were performed. The predictive performance of the radiogenomics model integrating significant clinical variables, RBML classifiers, and molecular features was evaluated using receiver operating characteristic curve analysis. Five radiomics features and two conventional MRI findings significantly stratified HNSCC patients into responders and non-responders. On WGCNA analysis, 809 genes showed a significant correlation with two radiomics features. Functional enrichment analysis suggested that our proposed radiomics features could reflect the T cell-mediated immune response and immune infiltration of HNSCC. The radiogenomics model showed the highest area under the curve (0.88[95%CI 0.75-0.96]) for predicting IC response, which was better than MRI findings(p=0.0407) or molecular features(p=0.004) alone, but showed no significant difference with that of RBML model (p=0.2254) in test cohort. Merging imaging phenotypes with transcriptomic data improved the prediction of IC response in HNSCC.

Neoadjuvant chemotherapy for organ preservation in sinonasal squamous cell carcinoma.

In this study, we aimed to evaluate the role of induction chemotherapy (IC) in the treatment of locoregionally advanced sinonasal squamous cell carcinoma (SNSCC). 130 patients who accepted IC between 2010 and 2022 were retrospectively reviewed. After IC, all the patients underwent chemoradiotherapy (CRT)/ radiotherapy (RT) or CRT/RT followed by surgery. We investigated the objective response to IC, the optimal treatment strategy, organ preservation, and long-term survival. Eighty-seven patients (66.9%) achieved a partial response after IC. 86% (27/43) of the patients who did not respond to the IC still presented a sensitive response to radiotherapy (χ2 = 9.26, p = 0.005). Patients who respond to IC could benefit from CRT/RT followed by surgery over other treatment modalities. The 3-year overall survival (OS), progression-free survival (PFS), locoregional-free survival (LRFS), and distant metastasis-free survival (DMFS) rates of61.2%, 51.3%, 52.1%, 58.1% for the IC response group were significantly superior to those of 37.3% (HR = 0.58, 95% CI 0.34-1.01, p = 0.030), 33.5% (HR = 0.49, 95% CI 0.30-0.82, p = 0.002), 35.9% (HR = 0.54, 95% CI 0.32-0.91, p = 0.009), 36.1% (HR = 0.60, 95% CI 0.35-1.03, p = 0.040) for the IC non-response group. Patients who responded to IC had a high rate of organ preservation compared with patients who did not respond to IC (90.8% vs. 74.4%, χ2 = 6.19, p = 0.013). The results demonstrated a response rate to IC in patients with advanced SNSCC; furthermore, the response to IC indicated better survival. Patients who responded to IC had a high rate of organ preservation.

Selective Treatment Deintensification by Reducing Radiation Dose and Omitting Concurrent Chemotherapy Based on Response to Induction Chemotherapy in Human Papillomavirus-Associated Oropharyngeal Squamous Cell Carcinoma: A Single-Arm, Phase 2 Trial (IChoice-01)

To demonstrate the feasibility of deintensification regimen in the light of the response to induction chemotherapy (IC) in human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC). Patients with p16+ OPSCC, T1-2/N1-3M0 (excluding T1N1M0 with single and ≤3 cm lymph node) or T3-4N0-3M0 were enrolled between January 2019 and July 2021. All patients received 2 cycles of IC with docetaxel 75 mg/m2 dL and cisplatin 75 mg/m2 dL every 3 weeks. Those with major responses (≥50% decrease in both primary and lymph nodes) to IC entered the deintensification cohort (cohort D), in which intensity modulated radiation therapy alone was given to a reduced dose of 60 Gy/30 fractions. Those who failed to meet major responsesentered the concurrent chemoradiotherapy cohort (cohort C), where the dose was simultaneously integrated boosted to a standard 70 Gy/35 fractions to nonmajor response sites, concurrently with cisplatin 80 mg/m2 dL,22. Patient-reported swallow function was documented using the MD Anderson Dysphagia Inventory. The primary endpoint was 2-year progression-free survival (PFS) using Simon's 2 stage design. A total of 26 of 48 (54.2%) participants met the criteria to enter cohort D and 22 of 48 (45.8%) patients entered cohort C. With a median follow-up time of 29.7 months (6.9-48.0 months), 2-year PFS and OS rates were 85.4% and 93.6%, respectively for all enrolled patients. In cohort D, 2-year PFS and OS rates were both 100%. Grade 3 and 4 IC-related toxicities included leukopenia/neutropenia occurring in 41.7% and hyponatremia in 4.2% of patients. A higher incidence of grade 3 and 4 mucositis (61.9% vs 23.1% P=.022) was observed in cohort C. Consistent decline in longitudinal MD Anderson Dysphagia Inventory scores were observed at month 3 after radiation therapy between cohorts and both were found to recover to baseline at month 12. Selective radiation therapy dose reduction and concurrent chemotherapy removal based on IC response in HPV+OPSCC was feasible and promising. Further study of this strategy to balance efficacy and toxicity is warranted in a prospective controlled trial.

Real-world analysis of D-RVd v. RVd at induction for newly diagnosed transplant eligible multiple myeloma patients.

e20024 Background: Daratumumab with lenalidomide, bortezomib, and dexamethasone (D-RVd) induction chemotherapy (IC) has recently been shown to improve depth of treatment response for transplant-eligible newly diagnosed multiple myeloma (NDMM) patients (pts) compared to RVd alone. The aim of this real-world data (RWD) retrospective study is to assess the efficacy and depth of response of D-RVd IC compared to RVd in transplant-eligible pts with NDMM. Methods: HealthTree Cure Hub for Multiple Myeloma (PMID: 35271305) an online portal for pts with plasma cell dyscrasias, was used to analyze validated RWD of 59 pts who received D-RVd to 121 pts with similar clinical characteristics but who received RVd at IC. Of the total 180 pts, 84 had completed IC and were at the initiation of maintenance (MT) at the time of this analysis. Patients that progressed prior to reaching MT or whose treatment deviated from the line of therapy (D-RVd/RVd IC, autologous stem cell transplant [ASCT], and MT, with or without consolidation) were also excluded. Response during MT was assessed using IMWG criteria. Results: From the 180 pts reviewed, 98 were excluded, 5 D-RVd and 10 RVD pts progressed before reaching MT, 11 D-RVd and 31 RVd pts deviated from the line of therapy, and 41 pts had not reached the MT phase at the time of the analysis. The remaining 84 pts (18 D-RVd pts and 64 RVd pts) were analyzed. Demographics and clinical characteristics were well-balanced between groups. The median age of both groups was 65 (range, 42-81), and over half were female (51%). The majority of pts (87%) had R-ISS stage I or II, and 45 pts (25%) had high-risk genetics (by mSMART 3.0). The overall response rate (ORR) was significantly higher for the D-RVd group compared to the RVd group at the initiation of MT (100% vs 62%; odds ratio, 22.4; P = 0.03). As assessed prior to the start of MT the depth of response was more favorable with D-RVd, with the odds ratio of achieving a VGPR or better at MT being significantly higher than RVd (89% to 58%; odds ratio (OR), 5.8; P = 0.03), complete response (CR) (78% to 47%; OR, 3.97; P = 0.03), stringent CR (sCR) (22% to 16%; OR, 1.5; P = 0.51), and minimal residual disease (MRD) negativity (17% to 11%; OR, 1.6; P = 0.51). With a median follow-up of 17 months for the D-RVd group (n = 18) and 29 months for the RVd group (n = 64), 0 events of disease progression occurred in the D-RVd group compared to 23 events in the RVd group. Median PFS was not reached in the D-RVd group and a Kaplan-Meier probability indicated a median PFS of 41 months for the RVd group. Conclusions: These data document improved response rate in transplant-eligible NDMM pts who received daratumumab with RVd as an IC therapy. D-RVd also improved PFS with significant differences between the two groups seen at 12 and 18 months. These results add to the accumulating data that the addition of daratumumab with RVd may be the new standard of care for the aforementioned patient population.

The smart options of induction therapy for locally advanced betel-nuts related HNSCC in Taiwan.

e18080 Background: The treatment of HNSCC in Taiwan is still very challenging and might be related to betel-nuts use. Betel nut chewing might contribute to strong angiogenesis/invasion and treatment refractoriness. In western countries where HPV+ oropharyngeal cancer prevalence is high, induction TPF (TAX323/324) response rate in locally advanced HNSCC is around 70%; Erbitux and TP (Argiris in JCO2008) induction response rate is 86%. In the analysis from KGMH in Taiwan, induction chemotherapy response for locally advanced HNSCC was 55% in betel-nuts chewers compared with 75% in non-users ( p=0.038; From Su in World Journal of Surgical Oncology 2016). In further studies from Taiwan, Avastin-PF induction benefit (ORR 80%) was also prominent from NTUH (Huang in ESMO Asia2016); Erbitux-TPF induction response rate was 88% from VGH by Lu in Head &amp; Neck2019. Neoadjuvant biochemotherapy seemed to bring more benefits in betel-nuts related HNSCC. In the era of incorporating immunotherapy to neoadjuvant setting of HNSCC, triple therapy of bio-chemoimmunotherapy deserves more attention. Methods: From 2012 to 2022, 111 unresectable stage IVA &amp; IVB betal-nuts related HNSCC patients (OSCC 69, Hypopharynx 26, OPC 13) had ever received induction Bio-chemotherapy or triple therapy (Bio-chemoimmunotherapy) in Yun-lin Branch of National Taiwan University Hospital. We have reviewed basic characteristics, therapeutic regimens, induction response, and final outcomes of these patients. Results: See table. Conclusions: Induction TPF response in locally advanced betel-nuts related HNSCC in Taiwan was not so prominent. Flexible chemotherapy backbones, such as TP/DP-HDFL(weekly docetaxel or paclitaxel with cisplatin and 24-hr high dose 5-fluorouracil/leucovorin infusion), might produce acceptable response rates with less toxicity. Bio(EGFR or VEGFR-targeting)-chemotherapy or Bio-chemoimmunotherapy has brought encouraging induction response with favorable toxicity profiles to conversion surgery or definite CCRT. Further investigation and clinical trials will be urgently warranted. [Table: see text]

Expert Recommendations for the Diagnosis, Treatment, and Management of Adult B-Cell Acute Lymphoblastic Leukemia in Latin America.

Despite strong induction chemotherapy response rates, only 30%-40% of patients with adult B-cell acute lymphoblastic leukemia (ALL) attain long-term remission. This study analyzes ALL in Latin America (LA) and recommends diagnosis, treatment, and management protocols. The Americas Health Foundation organized a panel of hematologists from Argentina, Brazil, Chile, Colombia, and Mexico to examine ALL diagnosis and therapy and produce recommendations. Lack of regional data, unequal access to diagnosis and therapy, inadequate treatment response, and uneven health care distribution complicate adult ALL management. The panel recommended diagnosis, first-line and refractory treatment, and post-transplantation maintenance. Targeted treatments, including rituximab, blinatumomab, and inotuzumab ozogamicin, are becoming available in LA and must be equitably accessed. This review adapts global information on treating ALL to LA. Governments, the medical community, society, academia, industry, and patient advocates must work together to improve policies.

Radiomics in Hypopharyngeal Cancer Management: A State-of-the-Art Review

(1) Background: Hypopharyngeal squamous cell carcinomas usually present with locally advanced disease and a correspondingly poor prognosis. Currently, efforts are being made to improve tumor characterization and provide insightful information for outcome prediction. Radiomics is an emerging area of study that involves the conversion of medical images into mineable data; these data are then used to extract quantitative features based on shape, intensity, texture, and other parameters; (2) Methods: A systematic review of the peer-reviewed literature was conducted; (3) Results: A total of 437 manuscripts were identified. Fifteen manuscripts met the inclusion criteria. The main targets described were the evaluation of textural features to determine tumor-programmed death-ligand 1 expression; a surrogate for microvessel density and heterogeneity of perfusion; patient stratification into groups at high and low risk of progression; prediction of early recurrence, 1-year locoregional failure and survival outcome, including progression-free survival and overall survival, in patients with locally advanced HPSCC; thyroid cartilage invasion, early disease progression, recurrence, induction chemotherapy response, treatment response, and prognosis; and (4) Conclusions: our findings suggest that radiomics represents a potentially useful tool in the diagnostic workup as well as during the treatment and follow-up of patients with HPSCC. Large prospective studies are essential to validate this technology in these patients.

Response to induction chemotherapy predicts survival outcomes in oropharyngeal cancer.

The role of induction chemotherapy (IC) in oropharyngeal squamous cell carcinoma (OPSCC) remains controversial. Its interpretation can be confounded by heterogeneity in chemosensitivity and human papillomavirus (HPV) status. This study aimed to investigate the prognostic impact of IC response in HPV-positive and -negative OPSCC. Patients with OPSCC who underwent IC and concurrent chemoradiotherapy (CCRT) were retrospectively analyzed. Radiologic response to IC by ≥50% was defined as IC-sensitive (IC-s), while lesser response was deemed as IC-resistant (IC-r). Progression-free survival (PFS) and overall survival (OS) were compared between subgroups. A total of 51 HPV-positive and 57 HPV-negative patients were included. IC-s patients accounted for 55.6%, 62.7%, and 49.1% in the entire cohort, HPV-positive, and HPV-negative subgroup, respectively. Compared with IC-r subgroup, IC-s was associated with better clinical outcomes either in the entire cohort (3y-PFS 91.7%vs.43.7%, P< 0.001; 3y-OS 98.3% vs. 67.4%, P= 0.002), the HPV-positive subgroup (3-year PFS 94.7% vs. 47.9%, P< 0.001; 3-year OS 100% vs. 73.5%, P=0.055) or the HPV-negative subgroup (3-year PFS 88.2% vs. 40.9%, P= 0.001; 3-year OS 96.4% vs. 63.1%, P=0.026). Multivariate analysis demonstrated that response to IC represents an independent prognosticator for 3-year PFS (HR, 0.088; 95% CI, 0.027-0.289; P < 0.001) and 3-year OS (HR, 0.100; 95% CI, 0.021-0.477; P=0.004). Response to IC exerts a critical predictive effect on prognosis of both HPV-positive and -negative OPSCC. Personalized treatment strategy based on IC response is worthy of further exploration in the future.

A dynamic nomogram combining tumor stage and magnetic resonance imaging features to predict the response to induction chemotherapy in locally advanced nasopharyngeal carcinoma.

To establish an effective dynamic nomogram combining magnetic resonance imaging (MRI) findings of primary tumor and regional lymph nodes with tumor stage for the pretreatment prediction of induction chemotherapy (IC) response in locoregionally advanced nasopharyngeal carcinoma (LANPC). A total of 498 LANPC patients (372 in the training and 126 in the validation cohort) with MRI information were enrolled. All patients were classified as "favorable responders" and "unfavorable responders" according to tumor response to IC. A nomogram for IC response was built based on the results of the logistic regression model. Also, the Cox regression analysis was used to identify the independent prognostic factors of disease-free survival (DFS). After two cycles of IC, 340 patients were classified as "favorableresponders" and 158 patients as "unfavorableresponders." Calibration curves revealed satisfactory agreement between the predicted and the observed probabilities. The nomogram achieved an AUC of 0.855 (95% CI, 0.781-0.930) for predicting IC response, which outperformed TNM staging (AUC, 0.661; 95% CI 0.565-0.758) and the MRI feature-based model alone (AUC, 0.744; 95% CI 0.650-0.839) in the validation cohort. The nomogram was used to categorize patients into high- and low-response groups. An online dynamic model was built ( https://nomogram-for-icresponse-prediction.shinyapps.io/DynNomapp/ ) to facilitate the application of the nomogram. In the Cox multivariate analysis, clinical stage, tumor necrosis, EBV DNA levels, and cervical lymph node numbers were independently associated with DFS. The comprehensive nomogram incorporating MRI features and tumor stage could assist physicians in predicting IC response and formulating personalized treatment strategies for LANPC patients. • The nomogram can predict IC response in endemic LANPC. • The nomogram combining tumor stage with MRI-based tumor features showed very good predictive performance. • The nomogram was transformed into a web-based dynamic model to optimize clinical application.

Induction Chemotherapy Response in Childhood Acute Lymphoblastic Leukaemia and its Correlation with Cytogenetic and Molecular Features.

To study the correlation of cytogenetic and molecular abnormalities on induction chemotherapy in childhood acute lymphoblastic leukaemia (ALL). Analytical study. Department of Haematology, Armed Forces Institute of Pathology (AFIP), from March 2021 to August 2021. Patients aged 1-18 years with newly diagnosed acute lymphoblastic leukaemia were inducted. Patients aged less than 1 year and more than 18 years were excluded from the study. The diagnosis was based on morphology, cytochemistry, flow cytometry, and cytogenetic/molecular analysis. Risk stratification was done on the basis of age, TLC, and cytogenetic/molecular defects. The UKALL 2011 protocol was used for treatment with regimen-A for standard risk and regimen-B for high-risk patients. Bone marrow was repeated on day 29 of induction therapy and blast percentage was assessed to establish post-induction remission. Association between cytogenetic / molecular abnormalities and post-induction remission status was analysed using chi-square test. There were total 142 patients with mean age of 6.4 + 3.6 years and a male- to-female ratio of 2.7:1. Immunophenotyping revealed 85.9% cases as B-cell ALL and 14.1% as T-cell ALL. The most frequent cytogenetic and molecular abnormalities were hyperdiploidy (19%), t(9;22)/BCR-ABL1(p190) (10.6%), complex karyotype (5.6%), E2A-PBX1 (8.5%), and TEL-AML1 (4.9%). A total of 127/142 (89.4%) achieved haematological remission after induction therapy with two deaths during induction therapy (1.4%). Post-induction remission rate in patients with favorable cytogenetic/molecular defects was 100% and in children with bad prognostic changes, the rate of remission was 69.2%. Chi-square test showed a significant association between cytogenetic/molecular abnormalities and post-induction remission (p-value <0.001). Cytogenetic and molecular abnormalities have a significant association with post-induction remission in children with acute lymphoblastic leukaemia. Acute lymphoblastic leukaemia, Cytogenetics, Chemotherapy, Induction, Remission.

Deep remission from induction chemotherapy predicts favorable long-term survivals in early stage extranodal nasal NK/T-cell lymphoma receiving sequential chemotherapy and radiation.

We aimed to assess the association between induction chemotherapy (CT) response and survivals and to explore an induction CT response-adapted treatment strategy for localized extranodal NK/T-cell lymphoma (NKTCL) receiving first-line sequential CT and radiation (RT). We retrospectively reviewed the data of patients with localized NKTCL receiving first-line CT+RT from 2010 to 2020 at two independent institutes (primary cohort, n = 203; validation cohort, n = 67). Responses after induction CT (initial response), RT (final response) and survivals were analyzed. Patients with initial complete remission (CR) had higher final CR rate than the others (99.1% vs. 78.7%, P < 0.001). Initial CR was associated with superior 5-year progression-free survival (PFS, 90.0% vs. 61.4% vs. 30.8%, P < 0.001) and overall survival (OS, 93.5% vs. 70.7% vs. 60.6%, P < 0.001), as compared to initial partial remission or non-response. Though majority of cases with initial non-CR achieved final CR after RT, they still had a tendency of shortened OS compared with initial CRs (86.9% vs. 90.6%, P = 0.063). Multivariate analysis demonstrated patients with initial non-CR had higher relapse (HR = 4.748, 95% CI, 2.396-9.407, P < 0.001) and death hazard (HR = 4.296, 95% CI, 1.802-10.24, P = 0.001). Furthermore, more intensive therapy of ≥6 total cycles of CT yielded significantly superior 5-year OS for patients with initial non-CR (76.7% vs. 54.7%, P = 0.026) rather than patients with initial CR. Deep remission from induction CT was associated with favorable survivals in localized NKTCL receiving CT+RT, and an induction CT response-adapted individualized treatment strategy might be recommended in clinical practice.