Use Of Induction Chemotherapy Research Articles

Post-operative complications following dose adaptation of intra-operative electron beam radiation therapy in locally advanced or recurrent rectal cancer.

The benefit of intra-operative radiotherapy (IORT) in the treatment of locally advanced rectal cancer (LARC) or locally recurrent rectal cancer (LRRC) lie in its ability to provide high-dose of radiation to limited at-risk volume, thereby eliminating microscopic disease and decreasing toxicity. A comparative study between high-dose-rate (HDR) brachytherapy, named intra-operative brachytherapy (IOBT), and intra-operative electron radiotherapy (IOERT) was performed showing favorable LRFS after IOBT, possibly due to a higher surface dose that is inherent in IOBT technique. The IOERT technique in Catharina Hospital Eindhoven was adapted to increase the surface dose, aiming to improve local control. Post-operative complications due to an increased radiation dose remain the matter of concern. This retrospective study was performed to compare complication rates before and after adapted IOERT dose. All patients undergoing surgery with IOERT for LARC or LRRC from September 2019 until July 2023, were considered. Patients selected until August 31, 2021 were included in control cohort (n = 108), and those chosen from September 1, 2021 onwards were included in intervention cohort (n = 92). Perioperative and (major) post-operative complications were classified retrospectively, during admission, at 30 days, and at 90 days. In LARC patients, a decrease in post-operative complications was observed (p = 0.009). 19% of LARC patients experienced major post-operative surgical complications, i.e., Clavien-Dindo grade 3b-5, regardless of treatment group. No difference in major 90-day complications was noted (p = 0.142). In LRRC patients, the use of induction chemotherapy decreased from 78% to 29% (p < 0.001), which complicated comparison. However, no difference in major post-operative complications was observed at 30 days (p = 0.222) or 90 days (p = 0.977) after surgery. Increased surface dose of IOERT does not seem to lead to an increase in post-operative complications. Further research is needed to evaluate the efficacy of dose adaptation in IOERT to improve local oncological control rates. Routine evaluation of CTCAE scores in follow-up will help uncover possible long-term radiation-induced toxicity.

Role of induction chemotherapy for locally advanced oral squamous cell carcinoma. A systematic review and meta-analysis based on the GRADE approach

ObjectiveA few reports have demonstrated the additional survival benefit obtained from induction chemotherapy. However, some facilities have differing opinions regarding the suitability of induction chemotherapy. The aim of this systematic review was to investigate the effectiveness of induction chemotherapy in patients with unresectable oral cancers without distant metastases. MethodsA comprehensive search of randomized controlled trials was conducted specifically targeting patients with primary unresectable oral cancer, defined as an intervention group (induction chemotherapy followed by chemoradiotherapy) and a control group (chemoradiotherapy alone). The electronic databases PubMed, Cochrane Central Register of Controlled Trials, and Ichushi-Web database were searched for relevant papers. The primary outcome was overall survival, and the secondary outcomes were progression-free survival and treatment-related deaths, all of which were judged to be of critical importance. Data available for integration were subjected to a meta-analysis, and the certainty of evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation approach. ResultsA search was conducted until February 2022, and four articles were included. The meta-analysis showed that the point estimates (95 % confidence interval) of the hazard ratios were 0.87 (0.74–1.01) for overall survival, 0.85 (0.75–0.97) for progression-free survival, and 0.98 (0.97–1.00) for treatment-related death. The certainty of the evidence for each item was very low. ConclusionLittle data are available to support the use of induction chemotherapy before chemoradiotherapy in patients with unresectable primary locally advanced oral cancer.

Proton beam therapy in multimodal treatment for locally advanced squamous cell carcinoma of the nasal cavity and paranasal sinus

BackgroundTo evaluate proton beam therapy (PBT) in multimodal treatment for locally advanced squamous cell carcinoma of the nasal cavity and paranasal sinus (NPSCC).MethodsThe cases in this study included T3 and T4 NPSCC without distant metastases that were treated at our center using PBT between July 2003 and December 2020. These cases were classified into 3 groups based on resectability and treatment strategy: surgery followed by postoperative PBT (group A); those indicated to be resectable, but the patient refused surgery and received radical PBT (group B); and those declared unresectable based on the extent of the tumor and treated with radical PBT (group C).ResultsThe study included 37 cases, with 10, 9 and 18 in groups A, B and C, respectively. The median follow-up period in surviving patients was 4.4 years (range 1.0-12.3 years). The 4-year overall survival (OS), progression-free survival (PFS), and local control (LC) rates were 58%, 43% and 58% for all patients; 90%, 70% and 80% in group A, 89%, 78% and 89% in group B; and 24%, 11% and 24% in group C. There were significant differences in OS (p = 0.0028) and PFS (p = 0.009) between groups A and C; and in OS (p = 0.0027), PFS (p = 0.0045) and LC (p = 0.0075) between groups B and C.ConclusionsPBT gave favorable outcomes in multimodal treatment for resectable locally advanced NPSCC, including surgery followed by postoperative PBT and radical PBT with concurrent chemotherapy. The prognosis for unresectable NPSCC was extremely poor, and reconsideration of treatment strategies, such as more active use of induction chemotherapy, may improve outcomes.

Cetuximab-Taxanes-Platinum-Fluorouracil/Capecitabine (C-TPF/C-TPX) – a Feasible Option for Recurrent HNSCC with Negative Prognostic Factors. Literature Review with a Case Presentation

Concurrent chemo-radiotherapy with Cisplatin is the standard treatment for locally advanced non-metastatic squamous cell carcinoma of the head and neck (HNSCC), but induction chemotherapy (IC) followed by chemo-irradiation, even controversial is a widely accepted option, especially in high-risk cases. A regimen including triple association (platinum-taxanes-fluorouracil) is generally considered superior in efficacy, but may be associated with severe toxicity. In the case of recurrence, the options are limited and the prognosis is generally unfavorable. Chemotherapy alone or in combination with an anti-EGFR monoclonal antibody (Cetuximab), immunotherapy or re-irradiation for selected cases are feasible options in loco-regional or metastatic repalapse. We present a case of nasopharyngeal cancer (NPC), with negative prognostic and predictive factors multimodally treated with an intensive chemotherapy regimen associating Cetuximab with a median survival higher than the median value reported in most studies. Replacing 5-Floururacil with Capecitabine and Cisplatin with Carboplatin may be an option to increase treatment tolerance and should be evaluated in randomized trials. The use of induction chemotherapy as a “new standard” before radio-chemotherapy for cases with negative prognostic factors should also be the subject of future studies. Re-challenge with platinum is also an option that needs to be re-evaluated.

Results of complex treatment of patients with locally advanced squamous cell carcinoma of the paranasal sinuses and nasal cavity using induction chemotherapy

Introduction. About 600 new cases of malignant neoplasms of the paranasal sinuses and nasal cavity are detected annually in Russia. To date, there are no randomized trials to determine the optimal treatment algorithm for this group of patients. Data on the use of induction chemotherapy in squamous cell carcinoma of sino-nasal tract are limited to a small series of clinical observations and, often, are retrospective in nature.Aim. Evaluation of the effectiveness of induction chemotherapy in patients with locally advanced squamous cell carcinoma of the paranasal sinuses and nasal cavity.Materials and methods. Since 2012, 22 patients with locally advanced cancer of the paranasal sinuses and nasal cavity have been treated in our center, who underwent 3-component induction chemotherapy according to the TPF protocol. Evaluation of the effectiveness of treatment was carried out according to the criteria of Response evaluation criteria in solid tumors 1.1 (RECIST 1.1). Patients with a decrease in the tumor size by 30 % or more, were followed by radiation therapy in doses of 66–70 Gy. Patients with a residual tumor underwent surgery after the end of chemoradiotherapy.Results. In 21 patients available for analysis, overall response rate after induction chemotherapy was 71 %: complete response was registered in 3 (14 %) patients, partial response in 12 (57 %), stable disease in 4 (19 %). Progression disease after 3 courses of induction chemotherapy was detected in 2 (10 %) patients.Conclusions. Thus, induction chemotherapy in patients with squamous cell carcinoma of sino-nasal tractseems to be a promising direction for investigation, that can significantly improve the long-term results of treatment of this category of patients and help to avoid of disabling surgery in some of them.

The Role of Induction Therapy for Sinonasal Cancers.

The role of induction chemotherapy in sinonasal cancers is promising; however, prospective studies with higher grades of evidence are needed. With the currently available literature, the authors would advocate for the use of induction chemotherapy (IC) in locally advanced sinonasal squamous cell carcinoma (T3-T4) for organ preservation and potentially for improved survival outcomes. In sinonasal undifferentiated carcinoma (SNUC), IC should be considered in all patients given its tendency for aggressive invasion and poor outcomes. In SNUC, response to IC may direct the modality of definitive treatment to follow. In responders (partial or complete), chemoradiation therapy should be strongly considered. In non-responders or in those with progression of disease, surgical therapy is favored. For esthesioneuroblastoma, surgical resection with negative margins and adjuvant radiation therapy remains the gold standard. However, IC may be considered for locally advanced disease especially with orbital invasion or in recurrent/distant disease. There is no definite indication for IC in sinonasal adenoid cystic carcinoma or sinonasal adenocarcinoma. Recommendations are summarized in Table 1.

Predictive Biomarkers for Response and Toxicity of Induction Chemotherapy in Head and Neck Cancers.

This review focuses on the molecular biology of head and neck squamous cell carcinomas and presents current and emerging biomarkers of the response of patients to induction chemotherapy. The usefulness of genes, proteins, and parameters from diagnostic clinical imaging as well as other clinicopathological parameters is thoroughly discussed. The role of induction chemotherapy before radiotherapy or before chemo-radiotherapy is still debated, as the data on its efficacy are somehow confusing. Despite the constant improvement of treatment protocols and the introduction of new cytostatics, there is still no consensus regarding the use of induction chemotherapy in the treatment of head and neck cancer, with the possible exception of larynx preservation. Such difficulties indicate that potential future treatment strategies should be personalized. Personalized medicine, in which individual tumor genetics drive the selection of targeted therapies and treatment plans for each patient, has recently emerged as the next generation of cancer therapy. Early prediction of treatment outcome or its toxicity may be highly beneficial for those who are at risk of the development of severe toxicities or treatment failure—a different treatment strategy may be applied to these patients, sparing them unnecessary pain. The literature search was carried out in the PubMed and ScienceDirect databases as well as in the selected conference proceedings repositories. Of the 265 articles and abstracts found, only 30 met the following inclusion criteria: human studies, analyzing prediction of induction chemotherapy outcome or toxicity based on the pretreatment (or after the first cycle, if more cycles of induction were administered) data, published after the year 2015. The studies regarding metastatic and recurrent cancers as well as the prognosis of overall survival or the outcome of consecutive treatment were not taken into consideration. As revealed from the systematic inspection of the papers, there are over 100 independent parameters analyzed for their suitability as prognostic markers in HNSCC patients undergoing induction chemotherapy. Some of them are promising, but usually they lack important features such as high specificity and sensitivity, low cost, high positive predictive value, clinical relevance, short turnaround time, etc. Subsequent studies are necessary to confirm the usability of the biomarkers for personal medicine.

Presurgical chemotherapy for HPV positive oropharyngeal squamous cancers.

e18022 Background: Human Papilloma Virus (HPV) related tumors of the oropharynx have been associated with an increase in survival for patients. Induction chemotherapy followed by surgery can maintain survival in select oropharyngeal squamous cancers (OPSCC) while avoiding radiotherapy, reducing overall treatment morbidity and deescalating treatment. In this study, all patients underwent planned induction chemotherapy and surgery with selective use of adjuvant, postoperative chemoradiotherapy (CRT). Methods: From 2008 to 2019, sixty-one patients with HPV positive oropharyngeal cancers were treated with induction chemotherapy followed by selective neck dissection and transoral resection of their primary disease. All patients were without distant metastasis at presentation. There were 56 men and 5 women with a mean age of 61 years. All patients were HPV+ via direct HPV immunohistochemistry (ISH). 44 patients were either never or long-term former smokers. 56 patients had primary disease in the tonsil, 4 in the base of tongue, 1 in the soft palate. 57/61 patients had nodal metastasis on presentation. All patients received induction chemotherapy inclusive of Cisplatin and Docetaxel (TP) of 2-4 cycles. 12 patients received either 5-FU or Cetuximab as well. Adjuvant chemoradiotherapy was deferred if patients had complete response (CR) to induction chemotherapy at the primary and neck, or with CR in the neck and partial response (PR) at the primary with negative surgical margins. Mean follow-up time was 3.2 years. Results: A CR to induction chemotherapy was achieved in 35/61 (57%) of patients. There were no treatment deaths or chemotherapy-related hospital admissions. 13/61 (21%) underwent adjuvant chemoradiotherapy. 14/61 (23%) patients with PR deferred chemoradiotherapy. 5 patients deferred chemoradiotherapy due to CR in the neck, 9 patients refused recommended chemoradiotherapy. 9/61 (15%) patients suffered recurrence of disease. Of these, 6 (67%) are currently free of disease (NED) as of most recent follow-up. Overall survival in this cohort was 95% (58/61), disease-free survival in this cohort was 85% (52/61). Smoking status (active vs former/non) was predictive of overall survival (p = .019). In total, 47/61 (77%) of patients were NED without undergoing chemoradiotherapy. Conclusions: This is a select series of patients with limited follow-up. However radiotherapy was avoided in most patients without sacrificing survival in this group with good overall prognosis. Appropriate use of induction chemotherapy and surgical management of oropharyngeal cancers is dependent upon the resectability of the primary on initial presentation (lack of significant local invasion). This study shows, for select HPV positive oropharyngeal cancers, induction chemotherapy followed by selective, trans-oral surgery allows for improved survival while avoiding the additional morbidity of (chemo)radiotherapy.

Definitive chemoradiotherapy +/- induction chemotherapy in esophageal cancer: A real-world experience.

e16072 Background: The SEER 5-year overall survival rate for all stages of esophageal cancer (EC) was 25% in 2019. Definitive chemoradiation (CRT) remains the primary treatment approach for locally advanced EC in the US, however, there are data to support use of induction chemotherapy (CT) in addition to CRT, particularly in adenocarcinoma (AC) histology. The purpose of our study was to assess outcomes in EC patients treated with definitive CRT (+/- induction) to determine which prognostic factors predicted for better survival in a recent, real-world cohort of patients, including those with limited stage IV disease. Methods: This retrospective study included Stages II-IVB (AJCC 8th ed.) EC patients treated with definitive CRT (radiation dose of ≥40 Gy and at least two cycles of concurrent CT [+/- induction CT, +/- esophagectomy]) at our institution between 2008 and 2020. To analyze prognostic factors and estimate OS, univariate models (UVA) and a multivariate (MVA) Cox proportional hazards regression model including age, Stage (II, III, IVA, IVB), AC vs. SCC, esophagectomy, ECOG performance status (PS), and induction CT were performed. Results: Of the 183 patients treated with definitive CRT, 18 were stage II, 119 stage III, 21 stage IVA, and 25 stage IVB. There were 45 SCC and 138 AC patients (Table). Prognostic factors associated with prolonged OS on MVA included lower PS (p&lt;0.01) and esophagectomy (p = 0.05). Stage IVA was associated with shorter survival (p&lt;0.01). Induction CT (delivered in 53% of AC, 31% SCC) was associated with improved survival on UVA (p=0.04), but not MVA (p = 0.08). By histology, 5-year survival rate was 42.7% and 18.2% for AC and SCC, respectively. Conclusions: At our institution, those who received an esophagectomy and those with lower ECOG scores had better survival. The 5-year survival rate was higher for AC patients compared to SCC, with more AC patients receiving esophagectomy and induction CT (significant on UVA, but not MVA). The 5-year survival rate for AC in our study was nearly identical to that seen in the CROSS trial (Shapiro et al. 2015) AC cohort but included &gt;25% stage IV patients. This modern cohort also included poor PS (ECOG≥2) patients (9.2% AC and 13.6% SCC), suggesting induction CT, in addition to pre-operative CRT + surgery, may have added benefit in a real-world practice. Thus, further prospective study is needed.[Table: see text]

Value of skull base invasion subclassification in nasopharyngeal carcinoma: implication for prognostic stratification and use of induction chemotherapy

ObjectivesPrognoses for nasopharyngeal carcinoma (NPC) between categories T2 and T3 in the Eighth American Joint Committee on Cancer (AJCC) staging system were overlapped. We explored the value of skull base invasion (SBI) subclassification in prognostic stratification and use of induction chemotherapy (IC) to optimize T2/T3 categorization for NPC patients.MethodsWe retrospectively reviewed 1752 NPC patients from two hospitals. Eight skull base bone structures were evaluated. Survival differences were compared between slight SBI (T3 patients with pterygoid process and/or base of the sphenoid bone invasion only) and severe SBI (T3 patients with other SBIs) with or without IC using random matched-pair analysis. We calculated the prognosis and Harrel concordance index (C-index) for the revised T category and compared IC outcomes for the revised tumor stages.ResultsCompared to severe SBI, slight SBI showed better 5-year overall survival (OS) (81.5% vs. 92.3%, p = 0.001) and progression-free survival (PFS) (71.5% vs. 83.0%, p = 0.002). Additional IC therapy did not significantly improve OS and PFS in slight SBI. The proposed T category separated OS, PFS, and locoregional recurrence-free survival in T2 and T3 categories with statistical significance. An improved C-index for OS prediction was observed in the proposed T category with combined confounding factors, compared to the AJCC T staging system (0.725 vs. 0.713, p = 0.046). The survival benefits of IC were more obvious in the advanced stage.ConclusionsNPC patients with slight SBI were recommended to downstage to T2 category. The adjustment for T category enabled better prognostic stratification and guidance for IC use.Key Points• For nasopharyngeal carcinoma (NPC) patients in T3 category, slight skull base invasion was a significant positive predictor for OS and PFS.• NPC patients with slight SBI might not gain significant survival benefits from induction chemotherapy.• Downstaging slight SBI NPC patients to T2 category would make a more accurate risk stratification, improve the predicting performance in OS, and have a better guidance in the use of IC for patients in advanced stage.

Clinical Profile and Treatment Outcomes in Patients Treated with Intensity-Modulated Radiotherapy (IMRT) for Carcinoma Nasopharynx: A Retrospective Analysis.

Objective To retrospectively evaluate the clinical outcome of carcinoma nasopharynx patients treated with the IMRT technique. Methods Eighty-one nasopharyngeal carcinoma patients who were treated with IMRT with or without chemotherapy between the period January 2011 and December 2014 at a comprehensive tertiary cancer center, Kerala, India, were included in the study. The mean age was 43 years (range 13–77 years), and majority of the patients were males (67.9%). The stagewise distribution of disease at presentation was 2 (2.5%) in stage I, 19 in stage II (23.5%), 31 (38.3%) in stage III, and 29 (35.8%) in stage IV. All patients were treated using simultaneous integrated boost (SIB) schedule using IMRT with 6 MV photon to a dose of 66 Gy in 30 fractions, 2.2 Gy per fraction prescribed to high-risk PTV; 60 Gy in 30 fractions, 2 Gy per fraction to intermediate risk PTV; and 54 Gy in 30 fractions, 1.8 Gy per fraction to low-risk PTV. Concurrent chemotherapy with cisplatin was offered to patients with stage II and above disease. Neoadjuvant chemotherapy with cisplatin and 5FU was given to patients with initially advanced disease (T3, T4, N2, and N3). Survival estimates were generated using the Kaplan–Meier method. The univariate analysis was performed using log-rank tests. Results The 5-year locoregional control (LRC), distant metastasis-free survival (DMFS), disease-free survival (DFS), and overall survival (OS) rates were 87.5%, 87%, 61.6%, and 62.5%, respectively. The 5-year OS was 100% for stage I (n = 2), 67% for stage II (n = 19), 70.4% for stage III (n = 31), and 68.1% for stage IV (n = 29). The DFS at 5 years was 100% for stage I, 61.1% for stage II, 56.2% for stage III, and 84.8% for stage IV disease. The univariate analysis showed that age, nodal stage, and use of induction chemotherapy showed an improved trend towards OS, though the results were not statistically significant. The predominant pattern of failure in the present study was distant metastasis. Most patients who developed distant metastasis in our study had either an advanced T stage or N3 disease at presentation. Conclusion The present study shows our initial experience with IMRT for nasopharyngeal carcinoma. The compliance to RT was good in this study. The 5-year LRC and OS rate of nasopharyngeal carcinoma patients treated with IMRT were 87.5% and 62.5%. Distant metastasis was the main pattern of failure.

Induction Chemotherapy for Advanced Oral Cavity Cancer.

Head and neck cancer is a heterogeneous disease, comprising multiple subsites with diverse etiologic factors, pathology and molecular features, response to treatment, and prognosis. Systemic treatment is usually incorporated in the management of locally advanced head and neck squamous cell carcinoma, and the use of induction chemotherapy has theoretical benefits on reducing the risk of distant metastasis, provide an in vivo testing of response and tumor biology and the potential to allow a more personalized and less toxic local treatment after downstaging. The aim of this review is to access the role of induction chemotherapy in patients with locally advanced oral cavity cancer. Clinical trials analyzing this treatment strategy in patients with resectable disease, followed by surgery, and in unresectable disease, followed by (chemo)radiotherapy or surgery are discussed, pointing out strengths and limitations of this data and highlighting the standard treatment in each clinical scenario. Future perspectives, including the incorporation of checkpoint inhibitors and biomarkers for patient selection are discussed. Surgery followed by (chemo)radiation is the standard of care for resectable oral cavity cancer patients, and chemoradiation is the standard for those considered as unresectable. Future trials with the incorporation of immunotherapy and better patient selection based on clinical and molecular biomarkers can bring new hopes for better therapeutic results in these patients.

Induction FOLFOX and PET-Directed Chemoradiation for Locally Advanced Esophageal Adenocarcinoma.

To compare the efficacy and safety of induction FOLFOX followed by PET-directed nCRT, induction CP followed by PET-directed nCRT, and nCRT with CP alone in patients with EAC. nCRT with CP is a standard treatment for locally advanced EAC. The results of cancer and leukemia group B 80803 support the use of induction chemotherapy followed by PET-directed chemo-radiation therapy. We retrospectively identified all patients with EAC who underwent the treatments above followed by esophagectomy. We assessed incidences of pathologic complete response (pCR), near-pCR (ypN0 with ≥90% response), and surgical complications between treatment groups using Fisher exact test and logistic regression; disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method and evaluated using the log-rank test and extended Cox regression. In total, 451 patients were included: 309 (69%) received induction chemotherapy before nCRT (FOLFOX, n = 70; CP, n = 239); 142 (31%) received nCRT with CP. Rates of pCR (33% vs. 16%, P = 0.004), near-pCR (57% vs. 33%, P < 0.001), and 2-year DFS (68% vs. 50%, P = 0.01) were higher in the induction FOLFOX group than in the induction CP group. Similarly, the rate of near-pCR (57% vs. 42%, P = 0.04) and 2-year DFS (68% vs. 44%, P < 0.001) were significantly higher in the FOLFOX group than in the no-induction group. Induction FOLFOX followed by PET-directed nCRT may result in better histopathologic response rates and DFS than either induction CP plus PET-directed nCRT or nCRT with CP alone.

P-265 Neoadjuvant radiotherapy for locally advanced rectal cancer during the first wave of COVID19 pandemic: Guy’s cancer cohort experience

The Covid-19 pandemic is a healthcare emergency with a significant impact on cancer services provision. In March 2020, our institution adopted the ESMO expert consensus guidelines for radiotherapy management of rectal cancer during the pandemic. Here we present short-term oncological outcomes of this approach compared to the same period in 2018. Patients who underwent neoadjuvant (chemo) radiotherapy for rectal cancer between 1st March 2020 and 31 May 2020 were identified from a research ethics committee (REC)-approved research database for cancer patients (Guy’s Cancer Cohort). Patient demographics and treatment characteristics were extracted and compared with a control cohort treated in the same period in 2018. The definition of local response was based on identification of downstaging on re-staging Magnetic Resonance Imaging (MRI) post neoadjuvant treatment (mrT3c/d-4 to mrT0-2 and mrT2 to mrT0-1) and classified in a binary format (response vs no response). In addition, in patients who underwent total mesorectal excision (TME), neoadjuvant rectal (NAR) score was calculated, as described previously, and classified into low (<8), intermediate (>=8<=16) and high (>16). The frequency of MRI and pathological response was compared using non-parametric Fisher exact test. Thirty patients were treated in the three-month period in 2020 as compared with 21 in 2018 (43% increase). No statistically significant differences were observed in baseline tumour characteristics. The use of neoadjuvant short-course radiotherapy (SCRT) treatment increased significantly from 19% of cases in 2018 to 50% during the pandemic, which was reflected in reduced radiotherapy-related hospital footfall (median 15 appointments in 2020 vs 25 appointments in 2018). While the use of concomitant fluoropyrimidines was lower (47 vs 71%), the use of induction chemotherapy was higher (30 vs 19%) in 2020 compared to 2018, which may reflect more prevalent use of total neoadjuvant treatment. There was no difference in the proportion of MRI responders between cohorts (52% in 2020 vs 38% in 2018). In patients who underwent TME, there was no difference in the proportion of R1 resection (0 in 2020 vs 9% in 2018), median NAR scores (8 (1-30) in 2020 v 15 (range 4-50) in 2018) or NAR score categories (22% good responders, 64% intermediate and 14% non-responders during Covid-19 vs 9% good responders, 55% intermediate and 36% non-responders in 2018). Changes in radiotherapy treatment of rectal cancer during Covid-19 pandemic, including more frequent use of SCRT (often in combination with neoadjuvant chemotherapy), did not seem to have negatively impacted short-term oncological outcomes, as measured by MRI downstaging rates and NAR scores following TME. The effect of the pandemic on medium and long-term oncological outcomes is still awaited.

The Outcome of Induction Chemotherapy, Followed by Neoadjuvant Chemoradiotherapy and Surgery, in Locally Advanced Rectal Cancer.

Background & Objective:Currently, neoadjuvant chemoradiotherapy, followed by surgery, is the standard treatment for locally advanced rectal cancer. The use of induction chemotherapy for this tumor is controversial. In this study, the benefits and side effects of induction chemotherapy in locally advanced rectal cancer are evaluated.Methods:Twenty-nine patients with locally advanced rectal cancer in 2018-2019 were enrolled in this study. Initially, they underwent induction chemotherapy (oxaliplatin 130 mg/m2 every 3 weeks and capecitabine 1000 mg/m2 twice a day for 14 days every 3 weeks for 2 courses). Then, neoadjuvant chemoradiotherapy (radiotherapy 50.4 Gy/28 for 5 days a week concomitant with weekly oxaliplatin 50 mg/m2, as well as capecitabine 825 mg/m2/bid on the days of radiotherapy) was administered. After 4 weeks, computed tomography (CT) scan of thorax, pelvis, and abdomen with and without contrast was performed. Total mesorectal surgery was performed 6-8 weeks after the end of radiotherapy. Four courses of adjuvant chemotherapy were applied. Pathologic complete response (pCR), margin, sphincter preservation, and adverse effects were assessed.Results:In this study, pCR was present in 6 (20.7%) patients. R0 resection was done in 96.05%. Sphincter was preserved in 44.4% of lower rectal tumors. Two patients (6.9%) did not complete adjuvant treatment. Grade 3 adverse effects were documented in 13.7% of cases during induction chemotherapy and 17.2% of cases during neoadjuvant chemoradiation. Mortality was not reported. Conclusion:Induction chemotherapy, followed by neoadjuvant chemoradiotherapy and surgery, would be an effective and safe modality in locally advanced rectal cancer.

Prevalence and distribution of cervical lymph node metastases in HPV-positive and HPV-negative oropharyngeal squamous cell carcinoma

ObjectiveIn oropharyngeal squamous cell carcinoma (OP-SCC), the prevalence and distribution of clinical and pathological lymph node metastasis in the neck have been extensively reported. It served as the basis for consensus recommendations on the selection of the lymph node levels in the neck requiring a treatment. The objective of the study is to compare the prevalence and distribution of neck node metastases in HPV+ and HPV− OP-SCC from a large series of patients with OP-SCC who underwent a cervical lymph-node dissection (LND) as part of their treatment. MethodsThe study concentrated on OP-SCC patients treated by various neck node dissection (LND) procedures from January 2014 to December 2018 in 3 French institutions. Patients with prior head and neck cancer, prior neck surgery, the use of induction chemotherapy, or patients with carcinoma of unknown primary were excluded. HPV-status was assessed by p16 immunohistochemistry. For each patient, the clinical and the pathological nodal status, as well as the distribution of the positive nodes in each neck level (from Ia to V) were reported. ResultsTwo-hundred and sixty-three patients were included (126 p16-negative (p16−), and 137 p16-positive (p16+). The rate of clinical positive node (cN+) reached 54% and 88.3% in the p16− and p16+ groups, respectively (p < 0.001); the corresponding rate of pathological positive node (pN+) reached 61.9% and 91.2%, respectively (p < 0.001). Regarding the clinical lymph node distribution, in p16+ patients, more positive nodes were observed in the ipsilateral level IV (p = 0.003), and less positive nodes were observed in the contralateral levels III and IV (p = 0.003 and p = 0.045, respectively). Regarding the pathologic lymph node distribution in the ipsilateral neck, in the cN0 patients, no significant difference was observed between p16− and p16+ patients (p = 0.33 to 1); in the cN+ patients, the nodes were distributed in levels Ib, II, III, IV and V without differences between the p16− and the p16+ patients. In the contralateral neck of p16− patients, nodes metastases were mainly observed in levels II, III and IV, whereas for the p16+ patients, positive nodes were only observed in level II (p = 0.03). ConclusionThis study demonstrated the higher prevalence of cN+ and pN+ in p16+ OP-SCC patients, but without meaningful difference in the distribution of the lymph node drainage between p16− and p16+ OP-SCC. It indicates that no difference should be made between p16− and p16+ patients regarding the extend of neck treatment.

Subjective functional outcomes in oropharyngeal cancer treated with induction chemotherapy using the MD Anderson Symptom Inventory (MDASI).

ObjectivesEvaluate the use of induction chemotherapy (IC) in oropharyngeal cancer (OPC) and its impact on subjective functional outcomes using a validated MD Anderson Symptom Inventory‐Head and Neck (MDASI‐HN) survey tool.MethodsA single institution retrospective review of OPC patients who received IC, including reasons given for using IC, regimens employed, responses, and patient‐reported outcomes (PRO). The latter included pain, distress, dysphagia, xerostomia, and feeding tube placement and dependency. PRO's were assessed using the validated MD Anderson Symptom Inventory‐Head and Neck (MDASI‐HN) conducted at baseline, during treatment, and at six‐month follow up.ResultsOne hundred and twenty‐five patients were evaluable. They were more likely to have large primary and/or bulky or low neck nodal disease as a reason for IC. A taxane‐containing regimen was most common. Primary tumor response was seen in 83.2% and the nodal response in 81.6%. Pain and xerostomia improved with IC, dysphagia was not adversely affected with IC. These symptoms all increased with consolidation chemoradiotherapy (CRT) but returned to baseline by 6 months post treatment. Feeding tube placement did not increase with IC but did with CRT, most patients were no longer feeding tube dependent at 6 months.ConclusionThis retrospective review of subjective functional outcomes, especially swallowing and feeding tube dependency, using the MDASI survey tool in 125 oropharyngeal cancer patients with large primary tumors and/or bulky adenopathy treated predominantly with platinum‐taxane based induction chemotherapy showed that such outcomes were not adversely impacted. While not standard, such approach may be beneficial in such patients.Level of Evidence2.

Roles of Clinical and Image-Based Features for Outcomes in Larynx Cancer Patients

In advanced larynx cancer, the use of induction chemotherapy (IC) to select patients for organ preservation offers outcomes comparable to upfront laryngectomy. Assessment of tumor response to IC is performed with direct laryngoscopy (DL), and barriers to this approach exist. In this study, we retrospectively investigate radiomic and clinical features as predictors of OS and laryngectomy free survival (LFS). Larynx cancer patients from a single institution with usable CT and PET scans were included. Clinical variables investigated were tumor subsite, T-stage, N-stage, neutrophil-lymphocyte ratio (NLR), and lymphocyte-monocyte ratio (LMR). CT-based variables were pre-IC GTV, GTV change between pre and post IC (ΔGTV), and 43 radiomic texture features. Cox proportional hazards was utilized for OS and LFS; logistic regression was used for IC response. Feature selection for each model was performed by identifying variables with a significant (p ≤ 0.05) Spearman rank. Model accuracy was assessed using the average concordance index from 100 iterations of stratified, 5-fold cross validation. Of 84 patents with CT, and clinical features, 5 features were found to have significant correlations with surgeon-assessed IC response: 3 texture-based radiomic features (coarseness, busyness, grey level nonuniformity (GLN)), ΔGTV, and N-stage. The latter 3 features contributed significantly to the final model (see table). For OS, only N-stage had significant correlation. For LFS, 8 features were found to have significant correlations, including 5 texture features (coarseness, busyness, strength, grey level variance (GLV), large zone emphasis (LZE)), NLR, LMR, and ΔGTV. Of these 8 features, 2 contributed significantly to the final model (see table). When including PET features for 54 patients, only LFS was found to correlate significantly with PET-based features. Of 12 features found to have significant correlation with LFS, 5 contributed significantly to the final model: PET contrast (hazard ratio (HR) = 1.70, p = 0.02), PET correlation (HR = 3790, p = 0.03), PET dissimilarity (HR = 1.20E-05, p = 0.048), ΔGTV (HR = 0.959, p = 0.001), and NLR (HR = 3.67, p = 0.04). The average concordance index for this model was 0.628 ± 0.149. In this study, we investigate the role of CT-based, PET-based, and clinical features as predictors for OS, LFS, and surgeon-assessed response to IC in a bioselection approach to larynx cancer. Initial results indicate that several features may have value as predictors for OS, LFS, and IC response. Due to limited data size, further studies with larger datasets are necessary to validate these results and further explore the potential of these variables.Tabled 1Abstract 2698; TableModelFeatureHazard/Odds ratiop-valueMean C-idxICGLN0.4750.0280.808 ± 0.099ΔGTV5.23< 0.001N-stage1.860.003OSN-stage1.8740.010.643 ± 0.102LFSΔGTV0.578< 0.001NLR2.740.0050.664 ± 0.101 Open table in a new tab

Sinonasal undifferentiated carcinoma: Institutional trend toward induction chemotherapy followed by definitive chemoradiation

Recent reports have investigated the nascent role of induction chemotherapy for sinonasal undifferentiated carcinoma (SNUC). The goal of this study was to ascertain trends in treatment pattern changes for SNUC at a single institution and design a treatment algorithm utilized at our institution. Retrospective chart analysis of 21 cases of SNUC from 2010 to 2018. Of 21 patients in this cohort, 18 (85.7%) presented with T4 disease, 7 (33.3%) presented with nodal disease, and 3 (14.3%) presented with distant metastasis. Since 2016, patients have been managed by induction chemotherapy followed by concurrent chemoradiation. To this point, patients treated with TPF induction chemotherapy followed by concurrent chemoradiation show no evidence of disease; however, the average follow up time is 16.8 months. The multimodality treatment for SNUC continues to evolve, as highlighted by this study, toward increased use of induction chemotherapy followed by chemoradiotherapy.

Induction chemotherapy followed by concurrent chemoradiotherapy versus CCRT for locally advanced hypopharynx and base of tongue cancer.

Background/AimsClinical trials have not consistently supported the use of induction chemotherapy (IC) for locally advanced head and neck squamous cell cancer. Hypopharynx and base of tongue (BOT) cancer has shown relatively poor survival. We investigated the role of IC in improving outcome over current chemoradiotherapy (CRT) in patients with hypopharynx and BOT cancer. MethodsTreatment-naïve patients with stage III/IV (M0) hypopharynx or BOT cancer were randomly assigned to receive CRT alone (CRT arm: cisplatin 100 mg/m2 on D1 3-weekly, two times plus radiotherapy 68.4 Gy/30 fractions on weekdays) versus two 21-day cycles of IC with TPF (docetaxel & cisplatin 75 mg/m2 on D1, and fluorouracil 75 mg/m2 on D1-4) followed by the same CRT regimen (IC arm). The primary endpoint was progression-free survival (PFS). ResultsThis study closed early after enrollment of 36 patients (19 in the CRT arm, 17 in the IC arm). After a median follow-up of 47.2 months, there was no significant difference in PFS: the median PFS was 26.8 months for the CRT arm and was not reached for the IC arm (p = 0.13). However, the survival curves were widely separated with a plateau after 3 years, suggesting a potential survival benefit from IC: 3-year PFS rates were 45% and 68%, and 3-year overall survival rates were 56% and 86%, in the CRT and IC arms, respectively. ConclusionsThis study failed to demonstrate that induction TPF chemotherapy improves survival in patients with BOT and hypopharynx cancer. However, it suggested a favorable outcome with IC to this population.