Locoregional Failure Research Articles

Metabolic activity determines survival depending on the level of lymph node involvement in cervical cancer

BackgroundTo assess the impact of PET/CT functional parameters on survival, locoregional, and distant failure according to the most distant level of lymph node [18F]FDG uptake in patients with locally advanced cervical cancer (LACC).MethodsRetrospective study including 148 patients with LACC treated with concurrent chemoradiotherapy after PET/CT and para-aortic lymph node (PALN) surgical staging. Two senior nuclear medicine physicians reviewed all PET/CT exams and retrieved tumor and lymph node metabolic parameters: SUVmax, MTV, TLG. Oncological outcomes according to metabolic parameters and level of lymph node spread on PET/CT were assessed.ResultsIn patients without lymph node uptake on PET/CT, high MTV values of the cervical tumor were associated with DFS (HR = 5.14 95%CI = [2.15–12.31]), OS (HR = 6.10 95%CI = [1.89–19.70]), and time to distant (HR = 4.73 95%CI = [1.55–14.44]) and locoregional recurrence (HR = 5.18 95%CI = [1.72–15.60]). In patients with pelvic lymph node (PLN) uptake but without PALN uptake on [18F]FDG-PET/CT, high MTV values of the cervical tumor were associated with DFS (HR = 3.17 95%CI = [1.02–9.83]) and OS (HR = 3.46 95%CI = [0.96–12.50]), and the number of PLN fixations was associated with DFS (HR = 1.30 95%CI = [1.10–1.53]), OS (HR = 1.35 95%CI = [1.11–1.64]), and time to distant (HR = 1.35 95%CI = [1.08–1.67]) and locoregional recurrence (HR = 1.31 95%CI = [1.08–1.59]). There was no significant association between cervical tumor metabolic or lymph node metrics and survival outcome in patients with PALN uptake.ConclusionsCervical MTV is more accurate than SUVmax to predict survival outcome in patients with locoregional disease confined to the pelvis and should be implemented in routine clinical practice. Prognostic value of metabolic metrics disappears with PALN uptake, which is associated with distant failure in nearly half of patients.Graphical

Survival outcomes of perineural spread in head and neck cutaneous squamous cell carcinoma.

AimTo present an institution's experience and survival outcomes for patients with head and neck cutaneous squamous cell carcinoma (HNcSCC) and perineural spread (PNS).MethodRetrospective study of patients with HNcSCC and PNS treated between January 2010 and August 2020 from the Sydney Head and Neck Cancer Institute database, Sydney, Australia; a high‐volume, tertiary, academic head and neck centre. Patient demographics, primary site, involved cranial nerves, treatment modality, loco‐regional failure and survival data were obtained.ResultsForty‐five patients were identified, of which 32 patients were male (71%). Mean age at diagnosis was 68.7 years (range 43–90). Median follow‐up was 16.1 months (range 1–107). The trigeminal nerve was most frequently involved (n = 30, 66.6%) followed by facial nerve (n = 13, 28.9%). Most patients underwent surgery followed by radiotherapy (n = 33, 73%) and eight received definitive radiotherapy. The median overall survival (OS) was 4.5 years (95% CI 3.71–5.38), median disease‐specific survival 5.1 years (95% CI 4.21–5.97) and median disease‐free survival (DFS) was 1.7 years (95% CI 1.11–2.22). The estimated 5‐year OS and DFS were 45% and 25%, respectively. Patients treated with surgery and adjuvant radiotherapy with a clear proximal nerve margin had favourable DFS (P = 0.035) and trended towards better OS (P = 0.134) compared with patients with an involved nerve margin. Patients treated surgically with involved proximal nerve margins had similar outcomes compared with patients with treated definitive radiotherapy (HR 0.80, 95% CI 0.29–2.22, P = 0.664).ConclusionThe likelihood of achieving a clear proximal nerve margin should be a strong consideration in the selection of appropriate patients for primary surgery

Rectosigmoid Cancer-Rectal Cancer or Sigmoid Cancer?

Objectives:We aimed to determine the optimal treatment for patients with locally advanced rectosigmoid cancers, and to determine whether this can be guided by distance from anal verge (AV) and/or anatomic landmarks such as the sacral promontory and peritoneal reflection (PR).Materials and Methods:We retrospectively reviewed patients with T3-T4 and/or node-positive rectosigmoid cancers who underwent surgery from 2006 to 2018 with available pelvic imaging. We included tumors at 9 to 20 cm from the AV on either staging imaging, or colonoscopy. Patients were stratified into those who received neoadjuvant therapy, and those who underwent upfront surgery. Comparisons of characteristics were performed using χ2 test and Fischer exact test. Locoregional failure (LRF) and overall survival were compared using Cox regressions and Kaplan-Meier analysis.Results:One hundred sixty-one patients were included. Ninety-seven patients had neoadjuvant therapy, and 64 patients had upfront surgery. Median follow-up time was 45.1 months. Patients who had neoadjuvant therapy had tumors that were higher cT stage (P<0.01) with more positive/close circumferential resection margins seen on imaging by radiologists (28.9% vs. 1.6%, P=0.015). The 2-year rate of LRF, distant metastases, or overall survival was not significantly different between the 2 groups. None of 15 patients with tumors below the PR treated with neoadjuvant therapy had LRF, but 1 (25%) of 4 patients with tumors below the PR treated with adjuvant therapy experienced LRF (P=0.05).Conclusions:Patients with tumors below the PR may benefit more from neoadjuvant therapy. The PR on imaging may be a reliable landmark in addition to the distance from the AV to determine the most appropriate treatment option.

Long-term survival of patients with central or > 7 cm T4 N0/1 M0 non-small-cell lung cancer treated with definitive concurrent radiochemotherapy in comparison to trimodality treatment

AbstarctBackgroundTo examine long-term-survival of cT4 cN0/1 cM0 non-small-cell lung carcinoma (NSCLC) patients undergoing definitive radiochemotherapy (ccRTx/CTx) in comparison to the trimodality treatment, neoadjuvant radiochemotherapy followed by surgery, at a high volume lung cancer center.MethodsAll consecutive patients with histopathologically confirmed NSCLC (cT4 cN0/1 cM0) with a curative-intent-to-treat ccRTx/CTx were included between 01.01.2001 and 01.07.2019. Mediastinal involvement was excluded by systematic EBUS-TBNA or mediastinoscopy. Following updated T4-stage-defining-criteria initial staging was reassessed by an expert-radiologist according to UICC-guidelines [8th edition]. Outcomes were compared with previously reported results from patients of the same institution with identical inclusion criteria, who had been treated with neoadjuvant radiochemotherapy and resection. Factors for treatment selection were documented. Endpoints were overall-survival (OS), progression-free-survival (PFS), and cumulative incidences of isolated loco-regional failures, distant metastases, secondary tumors as well as non-cancer deaths within the first year.ResultsAltogether 46 consecutive patients with histopathologically confirmed NSCLC cT4 cN0/1 cM0 [cN0 in 34 and cN1 in 12 cases] underwent ccRTx/CTx after induction chemotherapy (iCTx). Median follow-up was 133 months. OS-rates at 3-, 5-, and 7-years were 74.9%, 57.4%, and 57.4%, respectively. Absolute OS-rate of ccRTx/CTx at 5 years were within 10% of the trimodality treatment reference group (Log-Rank p = 0.184). The cumulative incidence of loco-regional relapse was higher after iCTx + ccRT/CTx (15.2% vs. 0% at 3 years, p = 0.0012, Gray’s test) while non-cancer deaths in the first year were lower than in the trimodality reference group (0% vs 9.1%, p = 0.0360, Gray’s test). None of the multiple recorded prognostic parameters were significantly associated with survival after iCTx + ccRT/CTx: Propensity score weighting for adjustment of prognostic factors between iCTx + ccRT/CTx and trimodality treatment did not change the results of the comparisons.ConclusionsPatients with cT4 N0/1 M0 NSCLC have comparable OS with ccRTx/CTx and trimodality treatment. Loco-regional relapses were higher and non-cancer related deaths lower with ccRTx/CTx. Definitive radiochemotherapy is an adequate alternative for patients with an increased risk of surgery-related morbidity.

High Failure Rates in Young Nonsmoker Nondrinkers With Squamous Cell Carcinoma of the Oral Tongue.

There has been a disproportionate increase in the incidence of young patients with squamous cell carcinoma of the oral tongue (SCCOT). The purpose of this study was to compare young patients to older patients with SCCOT without prior drinking or smoking history as this population is poorly characterized in the literature. A retrospective review of patients presenting to our institution with SCCOT was performed. The clinical and pathologic characteristics, as well as, outcomes were compared between younger patients (age ≤45) and older patients (age >45). Outcome analysis was performed using Kaplan Meier method. Multivariable Cox proportional hazard models were performed for age and stage. Eighty-two patients (38 young, 44 old) were included in this study. Median follow-up was 29.4 months. When compared to the older cohort (age >45), the younger cohort (age ≤45) demonstrated lower rates of 5-year locoregional control (LC) (79.6% vs. 52.5%, p=0.043) and distant metastasis-free survival (88.1% vs. 61.8%, p=0.006). Both cohorts demonstrated similar overall survival rates (55.5% vs. 58.1%) and disease-specific survival (66.2% vs. 58.1%). Of patients experiencing locoregional failure with available radiation therapy plans and PET scans in younger cohorts (n=7), 100% demonstrated in-field failures. Multivariable Cox proportional hazards demonstrated age was an independent predictor of DMFS (p=0.004) and the advanced stage was a predictor of DSS (p=0.03). Young, nondrinker, nonsmokers with SCCOT demonstrate high rates of locoregional recurrence, distant metastasis, and in-field failures. Future studies are warranted to determine underlying mechanisms driving pathogenesis in this unique cohort. 3 Laryngoscope, 133:1110-1121, 2023.

Abstract 203: The role of FOXM1 in senescence suppression and radiation resistance in oral cavity squamous cell carcinoma

Abstract INTRODUCTION: Advanced oral cavity squamous cell carcinoma (OCSCC) relies on surgery and radiation for cure; with ~30% experiencing locoregional failure. Earlier studies suggest OCSCCs resist radiation response by suppressing senescence. CDKN2A, coding for p16INK4a (p16), a CDK4/6 inhibitory protein, is among the most commonly lost tumor suppressors in OCSCC. Forkhead Box M1 (FOXM1) is an understudied key regulatory protein in OCSCC whose activation, similar to Rb, is controlled by CDK4/6. FOXM1 activity not only impacts cell proliferation, but also promotes DNA damage repair and suppresses senescence. The current study examines how FOXM1 signaling plays a critical role in resistance to radiation in OCSCC. We demonstrate that CDK4/6 inhibition improves radiosensitivity in OCSCC via senescence as a result of FOXM1 suppression. METHODS: Microarray data were analyzed to investigate FOXM1 levels in OSCC tumors. Basal FOXM1 levels in immortalized OCSCC cell lines (HN5 and Cal27) were evaluated using western blot. Cells were treated with palbociclib, radiation (RT), or combination (1µM palbociclib and 4 Gy (P+RT)) to examine the effects on senescence and FOXM1 signaling. β galactosidase colorimetric (β-gal) staining was used to evaluate senescence. Western blot was used to measure protein levels and QPCR to measure FOXM1 expression. To demonstrate senescence as a function of FOXM1 inhibition, knockdown assays (KD) were performed with siRNA targeting FOXM1. To further eliminate off target drug effects knockdown was also performed with siRNA targeting CDK4/6. RESULTS: FOXM1 was upregulated ~2.2-fold in OCSCC tumors vs. matched normal mucosa samples (N=43, p=2.85008E-06). FOXM1 protein was upregulated 7-fold (HN5) and 5-fold (Cal27) compared to normal oral keratinocytes (HOK16B). β-gal staining revealed a dose dependent senescence induction in OCSCC, where P+RT vs. RT showed a robust 5-fold (HN5) and 3-folds (Cal27) increase. Interestingly, FOXM1 protein and transcript expression doubled in samples treated with RT. P+RT vs. RT demonstrated a decrease in FOXM1 protein levels in HN5 (10-fold) and Cal27 (3-fold), with corresponding decreases in mRNA levels. Knockdown of FOXM1 induced senescence, which further increased when combined with radiation: siFOXM1+4 Gy resulted in 60% (HN5) and 50% (CAL27) β-gal positive cells. Compared to untreated controls, CDK4/6 KD demonstrated a 2.5 and 10-fold decrease in FOXM1 protein levels in HN5 and CAL27, respectively. Furthermore, a concurrent inhibition of CDK4/6 with RT not only resulted in a decrease in FOXM1 expression but also resulted in a near-complete senescence in treated cells (95% β-Gal staining). CONCLUSION: Suppressing FOXM1 directly or via CDK4/6 inhibition appears to make OCSCC more susceptible to RT via potentiating senescence. We propose inhibition of FOXM1 as a rational and potentially effective strategy to sensitize OCSCC to radiation. Citation Format: Nitisha Shrivastava, Yisrael Wallach, Daniel Li, Carlos Thomas, Michael B. Prystowsky, Indranil Basu, Chandan Guha, Thomas J. Ow. The role of FOXM1 in senescence suppression and radiation resistance in oral cavity squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 203.

International Consensus Guidelines for Adjuvant Radiation Therapy for Bladder Cancer After Radical Cystectomy: Update From an IBIS Workgroup

PurposeIn 2016, international consensus clinical target volume (CTV) guidelines for adjuvant radiation treatment after radical cystectomy in patients with muscle-invasive bladder cancer with high risk for locoregional failure (LRF) were published. A subsequent external validation study recommended several CTV optimizations (CTV-OPT). This study aimed to update international consensus guidelines based on new clinical experiences. Methods and MaterialsPhase 1 (delineation interobserver variability): Four observers delineated the CTV of 9 patients post radical cystectomy, as in clinical practice. Interobserver agreement in contouring was evaluated using volume- and κ-statistics. Phase 2 (pattern of failure analysis): Among a prospective cohort of 72 patients treated with adjuvant radiation treatment, 11 developed LRF (10 available for review). LRFs were mapped in predefined pelvic subsites (ie, common, external and internal iliac, obturator and presacral node regions, and cystectomy bed), and their distance to CTV-OPT was measured. The actual delivered dose at each relapse site was calculated. Phase 3 (review CTV): Based on the results of phase 1 and 2, 5 senior radiation-oncologists (International Bladder Investigator Society) reviewed the published CTV borders and provided an update when indicated. ResultsPhase 1: The mean overall κ-value was 0.66 (range, 0.60-0.70), indicating substantial overall agreement per Landis-Koch criteria. Specific κ-values per area indicated for the common iliac and obturator node regions only slight and moderate variability, respectively. Phase 2: Thirteen out of 16 LRFs centers were not included in the CTV-OPT. Ten LRF sites received a median dose <45 Gy, of which 6 were located in the cystectomy bed that was not included in the CTV because of negative radical cystectomy margins. Phase 3: Key recommendations by the panel were to include the entire common iliac node region and the cystectomy bed regardless of surgical margin status and a reaffirmation to not crop the CTV out of bowel. ConclusionsInternational consensus guidelines were updated.

P-238 Pattern of failure after radiotherapy for squamous cell carcinoma of the anus

Squamous cell carcinoma of the anus (SCCA) is primarily treated with radiotherapy (RT). Treatment failure is predominantly locoregional within the pelvic area. Information on the pattern of failure is important when optimizing treatment strategies. The aim of this study was to evaluated pattern of failure and outcome after radiotherapy for SCCA. A single center, retrospective study was conducted, including patients with histopathological proven SCCA diagnosed between 1998 and 2018 and treated with RT with curative intention. Data was collected from medical records and included patient-, disease-, and treatment characteristics, and outcome data. Disease stage was reclassified according to the 8th edition of the TNM staging system. Locoregional failure (LRF) was defined as failure within the pelvis, and distant failure (DF) as failure outside the pelvis. Survival data were estimated using the Kaplan-Meier method. In total 420 patients treated with curative RT were identified. Median age was 60 years (range 28-89), 75.0% were female, 68.8% had T1-T2 tumors, and 30.9% were diagnosed with lymph node (LN) positive disease. All patients received RT, RT only (79.8%) or with concomitant chemotherapy (19.3%), further 30.7% received induction chemotherapy. Treatment planning was done with IMRT/VMAT in 76.4% of cases, and median prescribed dose to tumor was 64Gy (range 45-64), 64Gy (range 50-64) to pathological LN and 51.2Gy (range 39-54) to the elective nodal areas. Median follow-up (FU) time was 6.1 years (range 0.05-23.6). Overall survival for all stages at 3- and 5 years was 84.0% and 75.5%, respectively and disease-free survival was 73.2% and 69.9% at 3 and 5 years. 85.9% (n=361) achieved complete response (CR) after RT whereas 13.8% (n=58) was diagnosed with progressive or persistent disease, of whom 94.8% had salvage surgery performed. Of patients with CR after RT 19.1% (n=69) experienced treatment failure during FU. As first site of recurrence 13.0% had LRF (n=47), 5.0% had DF (n=18), and 1.1% had both LRF and DF (n=4). When combining both persistent disease and later recurrence 30.2% experience treatment failure. In general, few regional LN recurrences were observed (1.7% of first failures including 0.6% with LN only failures). Recurrence in regional LN was located to the mesorectal LN (n=2), inguinal LN (n=3) or iliac LN (n=1). DF as first site of failure was seen in 22 cases (6.1%) located to either the lung (n=11), liver (n=7) distant LN (n=8), bone (n=1), brain (n=1) or other (n=2) with 8 patients having failure to more than one site. When looking at subsequent failures DF was seen in further 14 cases with a total DF rate of 8.6%. Recurrences to regional LN and DF were low, and the majority of recurrences were thus located within the standard irradiated area. Consequently, it is highly relevant to investigate the exact anatomical location and its relation to specific treatment dose. A dose-mapping study is therefore ongoing.

Association of plasma tumor tissue modified viral HPV DNA (TTMV) with tumor burden, treatment type, and outcome: A translational analysis from NRG-HN002.

6006 Background: NRG-HN002 was a phase II trial that randomized patients with p16-positive oropharynx cancer to 60 Gy IMRT with concurrent cisplatin (IMRT-C) or 60 Gy accelerated IMRT. The protocol specified plasma collection at pretreatment (t0), intratreatment (20-28 Gy, t1), and 2 weeks to 1 month posttreatment (t2); at these timepoints, TTMV was assayed. A prespecified analysis evaluated: association of t0 TTMV to gross tumor volume (GTV) of primary and lymph nodes; t0-t1 decrease in TTMV; and association of t2 TTMV to treatment and outcome. Methods: TTMV was quantified as fragments/mL of plasma. If TTMV-HPV16 was not detected (&lt;5 fragments/mL) or was a low value, the specimen was tested for TTMV-HPV18, -HPV31, -HPV33, and -HPV35. The distribution of t0 TTMV fragments was highly skewed, so these data were log-transformed; their correlation to GTV was measured by Pearson coefficient. Paired and two-sample t-tests were used to compare t0 and t1 log-transformed fragments within and between arms. Proportions of TTMV detection at t2 between arms were compared using Fisher’s exact test. Rates of undetectability and fragment clearance (≥94% reduction from t0) at t2 were estimated. The negative predictive value (NPV) was estimated for 2-year locoregional failure (LRF) and progression-free survival (PFS). Results: Of 306 eligible patients, 164 (53.6%) donated at least one specimen. The median collection time/RT dose was -2.6 days before RT (Q1-Q3, -4.0-0.0), at 24 Gy (22-28), and 25.5 days after RT end (18-31). The t0, t1, and t2 patient participation rates were 53.6%, 45.4%, and 42.5%. Zero TTMV fragments were detected in 10.4% at t0, 19.4% at t1, and 93.1% at t2. At t0, t1, and t2, 83.5%, 79.1%, and 6.2% had detectable TTMV; 78.0%, 73.4%, and 5.4% had TTMV-HPV16. In correlating GTV to t0 TTMV fragments, the Pearson coefficient was 0.30 (95% CI 0.15-0.44). In a linear model, T stage (p=0.01) and N stage (p=0.004) were positively associated with t0 TTMV fragments. On the IMRT-C arm, the t0-to-t1 mean change was -1.06 (p=0.0009), and for IMRT, it was -0.22 (p=0.35) (p=0.03 between arms). The t2 TTMV detectability rate was 3.3% for IMRT-C vs 8.7% for IMRT (p=0.28). The t2 TTMV undetectability rate was 93.8% and the fragment clearance rate was 95.4%. Two-year LRF and PFS were 6.2% and 91.4%. The NPV of t2 undetectability was 95.0% (95% CI 89.4-98.1) for 2-year LRF and 93.3% (95% CI 87.3-97.1) for 2-year PFS, and for fragment clearance was 94.3% and 92.7%. Conclusions: Feasibility of the TTMV-HPV assay in clinical trial specimens was established. About 10% of p16-positive patients had zero TTMV fragments at baseline. Among those with TTMV detectability, 6.6% had types other than TTMV-HPV16. T and N stage were positively associated with TTMV fragments. The IMRT-C arm achieved rapid TTMV undetectability unlike IMRT. The NPV of posttreatment undetectability was 93-95% for 2-year LRF and PFS.

Six-year follow-up from the weekly-three-weekly study comparing cisplatin once-a-week to once-every-three-weeks as concurrent chemoradiation for locally advanced head and neck squamous cell carcinoma.

6071 Background: In the weekly-3-weekly (W3W) study, cisplatin at 100 mg/m2 once-every-3-weeks led to superior locoregional control compared to cisplatin 30 mg/m2 once-a-week in combination with radical radiation for locally advanced head and neck squamous cell carcinoma (LAHNSCC). We report the updated analysis of the study. Methods: In this phase III open label non-inferiority study conducted between 2013 and 2017, 300 patients with LAHNSCC were randomly assigned to receive cisplatin 100 mg/m2 once-in-3-weeks or cisplatin 30 mg/m2 once-a-week, concurrently with radiation. The primary endpoint was locoregional control. Secondary outcomes included progression free survival (PFS), overall survival (OS), toxicity, and quality of life. Results: As of February 5, 2022 (median follow-up, 77.3 months), 132 patients (44%) have had an event for locoregional recurrence; 75 (50%) in the once-a-week cisplatin arm and 57 (38%) in the once-every-3-weeks cisplatin arm. The updated estimated cumulative 2-year locoregional control rates were 59.3% and 75.3% in the once-a-week and once-every-3-weeks cisplatin arms, respectively; absolute difference, 16% (95% CI, 7.19 to 24.81). The estimated 5-year locoregional control rates were 48.2% and 55.2% in the once-a-week and once-every-3-weeks cisplatin arms respectively; absolute difference, 7% (95% CI, -2.5 to 16.5). The median time to locoregional failure was 46.1 months (95% CI, 31.63 to 60.56) in the once-a-week cisplatin arm, and 57.9 months (95% CI, 47.1 to 68.6) in the once-every-3-weeks cisplatin arm; HR, 1.43 (95% CI, 1.01 to 2.02); P = 0.042. The estimated median PFS was 17.5 months (95% CI, 0 to 38.31) in the once-a-week cisplatin arm, versus 37.5 months (95% CI, 28.45 to 46.45) in the once-every-3-weeks cisplatin arm; HR, 1.13 (95% CI, 0.85 to 1.5); P = 0.41. Events for OS included 173 (57.7%) deaths; 109 (36.3%) patients are alive, and 18 (6%) are lost to follow-up. The 5-year OS in the once-a-week and once-every-3-weeks cisplatin arms were 43.1% and 48.6%, respectively. Estimated median OS was 38.5 months (95% CI, 16.3 to 60.7) in the once-a-week cisplatin arm, versus 57.3 months (95% CI, 38.6 to 75.9) in the once-every-3-weeks cisplatin arm; HR, 1.19 (95% CI, 0.89 to 1.6); P = 0.238. Details regarding chronic toxicities and second primaries will be presented. Conclusions: Long term follow-up confirms that cisplatin at 100 mg/m2 administered once-every-3-weeks concurrently with radical radiation for LAHNSCC leads to superior locoregional control and should remain the standard of care. The study was not powered to test for a difference in OS; OS was numerically higher in the once-every-3-weeks cisplatin arm, but the difference did not attain statistical significance. Clinical trial information: CTRI/2012/10/ 003062.

A change in surgical margin: do wider surgical margins lead to decreased rates of local recurrence in T1 and T2 oral tongue cancer?

The purpose of this study was to assess the impact of a change in macroscopic/surgical margin width upon histological margins and loco-regional failure in early oral tongue squamous cell carcinoma (OTSCC). In 2009, the surgical margin protocol was increased from 10 mm to 15 mm. A retrospective review was performed of all patients who underwent treatment for early OTSCC between 2009 and 2016 with a 15-mm surgical margin (n = 142), and these patients were compared to those treated between 1999 and 2008 with a 10-mm surgical margin (n = 78). There was a significant increase in the rate of clear histological margins (P < 0.001). The rates of close (P = 0.002) and involved (P < 0.001) histological margins decreased significantly. There were significant reductions in local (P < 0.001) and regional (P < 0.001) recurrence rates. This study demonstrated that a surgical margin of 15 mm delivered significantly lower rates of close/involved histological margins and improved local and regional disease recurrence in early OTSCC when compared with a surgical margin of 10 mm.

Patterns of failure after salvage chemoradiotherapy for postoperative loco-regional recurrent esophageal cancer: 20-year experience in a single institution in Japan

The purpose of the present study was to evaluate patterns of recurrence after salvage chemoradiotherapy (SCRT) for postoperative loco-regional recurrent esophageal cancer. We reviewed records for 114 patients with postoperative loco-regional recurrent esophageal cancer treated by platinum-based chemoradiotherapy between 2000 and 2020, and we evaluated the patterns of failure in patients who had recurrence again or who had been observed for 2years or more after SCRT at the last observation date. One hundred and three patients were enrolled in this study. The median observation period for survivors was 60months. Fifty-three patients died of esophageal cancer and nine patients died of other diseases. The 5-year overall survival rate, cause-specific survival rate and disease-control rate were 43.7%, 45.3% and 37.0%, respectively. Sixty-five patients had failure after SCRT. In those patients, 26 patients had only distant organ or non-regional lymph node metastases, 26 patients had only loco-regional failure, and 13 patients had both. Of those 65 patients, 64 patients showed failure within 42months after SCRT. Of 39 patients with loco-regional failure, failure in the irradiated field was observed in 28 patients. Of those 28 patients, 27 patients showed failure within 24months and the other patient showed failure at 26.5months. The patterns of failure after SCRT for patients with postoperative loco-regional recurrent esophageal cancer were shown. The patterns of failure suggest that follow-up for at least 4years after SCRT should be performed for those patients.

The COMPLETE trial: HolistiC early respOnse assessMent for oroPharyngeaL cancEr paTiEnts; Protocol for an observational study

IntroductionThe locoregional failure (LRF) rate in human papilloma virus (HPV)-negative oropharyngeal squamous cell carcinoma (OPSCC) remains disappointingly high and toxicity is substantial. Response prediction prior to or early during treatment...

PO-1262 Early response to chemotherapy as predictor of locoregional and distant failure in NSCLC

PO-1262 Early response to chemotherapy as predictor of locoregional and distant failure in NSCLC

OC-0435 Loco-regional failure is associated with the stem cell marker SLC3A2, volume and HPV/p16 in HNSCC

OC-0435 Loco-regional failure is associated with the stem cell marker SLC3A2, volume and HPV/p16 in HNSCC

Predictors of Locoregional Recurrence in Oral Squamous Cell Carcinoma

Introduction: Lip and oral cavity cancer is the third and fifth most frequent cancer for men &amp; women respectively in Bangladesh. Locoregional recurrence after primary surgery is common for oral cancer due to aggressive local invasion and metastasis. The objective of this study was to analyze the predictors of locoregional failure in a tertiary center hospital. Materials and Methods: A prospective cohort study was designed to analyze the presence of recurrences of OSCC patients after surgery. The purposive sampling technique was used to include patients in the study. Excision of the primary tumor was done with neck dissection followed by reconstruction with local or regional flap. The variables considered were demographic information, site, TNM stage at diagnosis, margin status, lymph node metastasis, perineural invasion, recurrence, and the adjuvant therapy used for disease control. Patients were followed up by hospital revisits or phone calls and necessary information was collected through a standardized data collection sheet. Results: A total of 39 patients were included for data analysis. The male to female ratio was 1:2 and the most common primary site was mandibular alveolar mucosa (31%). Nearly 90% of patients were admitted with stage ׀׀׀ or ׀ᴠ lesions and tumor margin was positive in 21% of cases. Lymph node metastasis and perineural invasion were identified in 64% and 23% of cases respectively. Recurrence developed in 14 patients (36%) during the average follow-up of 13 months. Recurrences were more common in females (42%) and Postoperative histopathology showed a positive margin, perineural invasion, and N3 neck node. Univariate logistic regression analysis for locoregional recurrence showed no significant association between the variables and recurrence. Patients with clinically palpable lymph node, grade 2 lesion, presence of perineural invasion, presence of co-morbidity, patients who did not receive any adjuvant therapy, and patients who had metastatic neck node showed an increased odds ratio (OR&gt;1). Conclusion: The clinicopathologic and treatment-related factors of recurrence in OSCC were explored in this study. Although no significant association was identified between the variables and recurrence of lesions, a high recurrence rate was observed in a shorter span of the follow-up period. Update Dent. Coll. j: 2022; 12 (1): 12-16

Olfactory Neuroblastomas: What Actually Happens in the Long-Term?

Objective: The aim of this study was to investigate the long-term oncologic outcome and review the state of the art in the management of olfactory neuroblastomas. Material and Methods: The records of all patients treated for olfactory neuroblastomas in two academic departments between 1975 and 2012 were evaluated retrospectively. Data on epidemiological parameters were collected (age, gender), along with staging (Kadish, Morita), histologic grading (Hyams), time and form of treatment, locoregional control, and disease-specific and overall survival. Patients with other malignant diseases, distant metastases of olfactory neuroblastomas at the time of initial diagnosis, a follow-up time of less than 5 years, or insufficient clinical-pathological data were excluded from further analysis. Results: In total, 53 cases made up our final study sample (26 men, 27 women; male–female ratio 0.96:1). Their mean age was 48.6 years (range: 10–84 years). The mean follow-up time was 137.5 months (4–336 months, SD: 85.0). A total of 5 out of 53 study cases (9.4%) showed metastatic involvement of the neck at the time of initial presentation. Local recurrence was detected in 8/53 (15.1%) and regional recurrence in 7/53 of our study cases (13.2%). Three patients (42.8%) from the group of cases with surgery as the sole form of management (7/53, 13.2%) died due to the disease. The cumulative disease-specific survival and overall survivalfor the whole group of patients were 88.6% and 63.6%, respectively. The cumulative disease-specific survival stratified by Kadish A/B vs. Kadish C/D as well as Hyams I/II vs. Hyams III/IV showed superior results for limited tumors, albeit without significance, and low-grade tumors (highly significant difference). Conclusion: Craniofacial or sometimes solely endoscopically controlled resection can warrant resection of the olfactory neuroblastoma with wide margins. However, locoregional failures and distant metastases can occur after a long period of time. The non-negligible incidence of regional recurrences, partly in unusual localizations, leads us to consider the need to identify the “recurrence-friendly” cases and to perform individualized elective irradiation of the neck in cases with high-risk features.

Disparities in time to start of definitive radiation treatment for patients with locally advanced cervical cancer

BackgroundChemoradiation or radiation therapy alone are curative standards for patients with locally advanced cervical cancer.ObjectiveTo investigate factors that influence time to initiation of chemoradiation or radiation and the subsequent impact...

Predicting outcomes for locally advanced rectal cancer treated with neoadjuvant chemoradiation with CT-based radiomics

A feasibility study was performed to determine if CT-based radiomics could play an augmentative role in predicting neoadjuvant rectal score (NAR), locoregional failure free survival (LRFFS), distant metastasis free survival (DMFS), disease free survival (DFS) and overall survival (OS) in locally advanced rectal cancer (LARC). The NAR score, which takes into account the pathological tumour and nodal stage as well as clinical tumour stage, is a validated surrogate endpoint used for early determination of treatment response whereby a low NAR score (< 8) has been correlated with better outcomes and high NAR score (> 16) has been correlated with poorer outcomes. CT images of 191 patients with LARC were used in this study. Primary tumour (GTV) and mesorectum (CTV) were contoured separately and radiomics features were extracted from both segments. Two NAR models (NAR > 16 and NAR < 8) models were constructed using Least Absolute Shrinkage and Selection Operator (LASSO) and the survival models were constructed using regularized Cox regressions. Area under curve (AUC) and time-dependent AUC were used to quantify the performance of the LASSO and Cox regression respectively, using ten folds cross validations. The NAR > 16 and NAR < 8 models have an average AUCs of 0.68 ± 0.13 and 0.59 ± 0.14 respectively. There are statistically significant differences between the clinical and combined model for LRFFS (from 0.68 ± 0.04 to 0.72 ± 0.04), DMFS (from 0.68 ± 0.05 to 0.70 ± 0.05) and OS (from 0.64 ± 0.06 to 0.66 ± 0.06). CTV radiomics features were also found to be more important than GTV features in the NAR prediction model. The most important clinical features are age and CEA for NAR > 16 and NAR < 8 models respectively, while the most significant clinical features are age, surgical margin and NAR score across all the four survival models.

Germline Variants in Angiogenesis-Related Genes Contribute to Clinical Outcome in Head and Neck Squamous Cell Carcinoma.

Simple SummaryA high risk of relapse and treatment resistance are among the major challenges in locally advanced head and neck squamous cell carcinoma (HNSCC). Data show that common germline alterations in genes regulating angiogenesis may modulate treatment sensitivity, cancer progression, and prognosis, but relatively little is known about their role in HNSCC. Thus, our goal was to examine the effect of variation in these genes on survival outcomes in HNSCC patients receiving radiotherapy and cisplatin-based chemoradiotherapy. We identified genetic variants significantly affecting therapy results, constituting independent prognostic factors in these patients. Our results suggest that some polymorphisms in angiogenesis genes may be determinants of treatment efficacy and tumor aggressiveness in HNSCC, which may be of importance in standard therapy. These findings emphasize the potential value of the host genetic profile related to angiogenesis in assessing the risk of treatment failure.Fibroblast growth factor (FGF)/FGF receptor (FGFR), and platelet-derived growth factor (PDGF)/PDGF receptor (PDGFR) systems, as well as some matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), are involved in various steps of angiogenesis. Data indicate that common germline variations in angiogenesis-regulating genes may modulate therapy results and cancer progression. However, whether these variants affect clinical outcome in head and neck squamous cell carcinoma (HNSCC) is unclear. Hence, we assessed the relationship between FGF/FGFR, PDGF/PDGFR, MMP, and TIMP genetic variants and treatment outcomes in HNSCC patients receiving radiotherapy (RT) alone or combined with cisplatin-based chemotherapy. In multivariate analysis, FGF2 rs1048201 CC homozygotes showed a higher risk of death (p = 0.039), while PDGFRA rs2228230 T was strongly associated with an increased risk of locoregional relapse (HR 2.49, p = 0.001) in the combination treatment subgroup. In the RT alone subset, MMP2 rs243865 TT carriers had a higher risk of locoregional recurrence (HR 2.92, p = 0.019), whereas PDGFRB rs246395 CC homozygotes were at increased risk of metastasis (HR 3.06, p = 0.041). The MMP2 rs7201 C and TIMP2 rs7501477 T were associated with a risk of locoregional failure in the entire cohort (p = 0.032 and 0.045, respectively). Furthermore, rs1048201, rs2228230, rs246395, rs243865, rs7201, and rs7201/rs7501477 were independent indicators of an unfavorable outcome. This study demonstrates that the FGF2, PDGFRA, PDGFRB, MMP2, and TIMP2 variants may contribute to treatment failure and poor prognosis in HNSCC.