Primary Chemoradiation Research Articles

Does Bulky Adenopathy in Human Papilloma Virus-Positive Oropharyngeal Squamous Cell Carcinoma Require a Planned Post-Treatment Neck Dissection for Occult Residual Disease?

A planned neck dissection was traditionally considered for a large nodal disease after definitive chemoradiation, yet controversy exists for the human papilloma virus-positive oropharyngeal squamous cell carcinoma (HPV OPSCC). We aimed to measure the frequency of persistent occult neck disease in planned neck dissection for HPV OPSCC presenting with a large (≥3.0cm) nodal burden. We designed a retrospective cohort study at a single tertiary referral institution. The study population was sampled from 2006 to 2018 and subjects with HPV OPSCC and adenopathy ≥3.0cm. Inclusion criteria encompassed subjects who completed primary chemoradiation therapy (CRT) or primary radiation therapy (RT), and subsequently underwent a planned neck dissection. We excluded subjects who did not complete therapy or had less than 1-year follow-up. Our primary predictor variable was the size of cervical adenopathy on presentation (3.0-3.9cm, 4.0-4.9cm, 5.0-5.9cm, and ≥6.0cm). Our primary outcome of interest was the presence of disease based on the histopathology review. Other variables included the demographics, primary treatment with CRT or RT, and post-treatment clinical or radiographic evidence of disease. Chi-square testing was used to compare rates of persistent disease, with varying sizes of cervical adenopathy on presentation. The alpha level for statistical significance was set at 0.05. A total of 86 subjects were analyzed, with forty-one females and forty-five males, ranging from 36 to 77years (mean 54.6years). From the total study sample, 35% showed persistent disease, and 67% of those subjects had occult disease at the time of planned neck dissection. Greater than 20% of subjects had persistent disease when the nodal burden was ≥3.0cm at presentation. Furthermore, there was a statistically significant difference in the rates of persistent microscopic disease among subjects with nodal burden of different sizes based on chi-square testing (P=.01, χ2=10.66). Our data suggest that subjects with HPV OPSCC presenting with a nodal burden ≥3.0cm are likely to have 23% chance of persistent occult neck disease after primary CRT or RT. These findings may support the routine treatment of these subjects with a planned neck dissection after initial therapy to confirm or surgically complete disease eradication.

Five-year survival outcomes in oropharyngeal squamous cell carcinoma following transoral laser microsurgery.

To determine the 5-year survival outcomes of patients with oropharyngeal cancer treated with transoral laser microsurgery at our institution. A prospective longitudinal cohort study of all cases of oropharyngeal squamous cell cancer or clinically unknown primaries diagnosed at our institution between September 1, 2014, to December 31, 2019, treated with primary transoral laser microsurgery were analyzed. Patients with a previous history of head and neck radiation were excluded from analysis. Kaplan-Meier survival curves were used to estimate 5-year overall survival, disease-specific survival, local control, and recurrence free survival rates in oropharyngeal squamous cell carcinoma. Of 142 patients identified, 135 met criteria and were included in the survival analysis. Five-year local control rates in p16 positive and negative disease were 99.2% and 100%, respectively, with one locoregional failure in the p16 positive cohort. Five-year overall survival, disease-specific survival, and recurrence free survival in p16 positive disease were 91%, 95.2%, and 87% respectively (n= 124). Five-year overall survival, disease-specific survival, and recurrence free survival in p16 negative disease were 39.8%, 58.3%, and 60%, respectively (n= 11). The permanent gastrostomy tube rate was 1.5% and zero patients received a tracheostomy at the time of surgery. One patient (0.74%) required a return to the OR for a post-operative pharyngeal bleed. Transoral laser microsurgery is a safe primary treatment option for oropharyngeal squamous cell carcinoma with high 5-year survival outcomes, notably in p16 positive disease. More randomized trials are needed to compare survival outcomes and associated morbidity in transoral laser microsurgery compared to treatment with primary chemoradiation. 3.

Plasma sICAM-1 correlates with tumor volume before primary radiochemotherapy of head and neck squamous cell carcinoma patients.

Biomarkers are of major interest to optimize diagnosis, prognosis and to guide treatment in head and neck cancer patients. Especially blood-based biomarkers appear promising as they can be easily collected and repeatedly analyzed during the course of radiochemotherapy. At first, for a broad overview, multiple immune markers were evaluated in six plasma samples of three head and neck squamous cell carcinoma (HNSCC) patients at the beginning and the end of radio-chemotherapy. In this pre-selection, the soluble Intercellular Adhesion Molecule 1 (sICAM-1) appeared most promising. Thus, this marker was measured in multiple samples (n = 86) during treatment and follow-up in a cohort of eleven patients and correlated with tumor features and clinical data. We found a strong correlation between the initial levels of sICAM-1 in the plasma and the gross tumor volumes of the primary tumor and the involved lymph nodes. However, during the course of treatment no systematic dynamics could be identified. Toxicity or infections did not seem to influence sICAM-1 concentrations. sICAM-1 appears to reflect the pre-treatment total tumor burden (primary tumor and involved lymph nodes) in head and neck tumor patients. However, it does not seem to be a dynamic marker reflecting response during radiochemotherapy. Thus, if our findings are confirmed in future, sICAM-1 could be used as a staging marker: if high sICAM-1 levels but low tumor burden are found it might be reasonable to intensify staging investigations to rule out further, yet undetected, tumor sites.

The role of nutritional support in treatment of head and neck tumors: clinical case

The article presents a clinical observation of treatment of locally advanced squamous cell oropharyngeal carcinoma. The problems of nutritional support of patients during primary chemoradiation treatment are considered. The presented clinical case shows that use of sip feeds can significantly improve nutritional condition in patients with head and neck tumors and improve tolerability and results of antitumor treatment.

Treatment outcomes of primary surgery versus chemoradiotherapy for T4 oropharyngeal cancers

Concurrent chemoradiotherapy (CCRT) has been the standard of care for locally advanced diseases regardless of human papillomavirus infection status. Other treatment options include surgery followed by adjuvant therapy and induction chemotherapy followed by CCRT or radiotherapy. However, for locally advanced T4 laryngeal or hypopharyngeal diseases, surgery is preferred over CCRT. Given the improvement in the functional outcomes of surgery, examining the oncologic outcomes in OPSCC patients is critical. This study aimed to determine whether differences in overall survival (OS) exist between surgery and CCRT. Oropharyngeal cancer patients included in the cancer registry of our hospital from January 2014 to December 2018 were retrospectively analyzed. Patients with T4 disease who underwent curative treatment were identified. In this study, the primary and secondary outcomes were OS and disease-free survival (DFS), respectively. Potential confounding factors were also evaluated. Details regarding recurrence pattern were listed. From 2014 to 2018, 74 newly diagnosed oropharyngeal cancer patients were identified from our cancer registry database, 60 of whom satisfied our inclusion criteria. Our findings showed an OS of 25.5 months and DFS of 17.5 months. No significant difference in both of OS and DFS were observed between the surgery and CCRT cohorts. Sex, stage, second primary cancer, IC, and primary treatment were not correlated with DFS. Male sex was the only significant factor identified, with an HR of 0.2 for OS (95% confidence interval, 0.06-0.71). No significant difference in both OS and DFS were observed between the CCRT and surgery cohorts. CCRT remains the standard of care for locally advanced disease.

Prognostic Impact of Caspase-8, CDK9 and Phospho-CDK9 (Thr 186) Expression in Patients with Uterine Cervical Cancer Treated with Definitive Chemoradiation and Brachytherapy.

Introduction: After primary platinum-based chemoradiation of locally advanced uterine cervical cancer, a substantial proportion of women present with persistent, recurrent or metastatic disease, indicating an unmet need for biomarker development. Methods: We evaluated the clinical records of 69 cervical cancer patients (Federation of Gynecology and Obstetrics, FIGO Stage > IB3) who were subjected to definitive CRT. Immunohistochemical scoring of caspase-8, cyclin dependent kinase 9 (CDK9) and phosphorylated (phospho-)CDK9 (threonine (Thr) 186) was performed on pretreatment samples and correlated with the histopathological and clinical endpoints, including relapse-free survival (RFS), distant metastasis-free survival (DMFS), cancer-specific survival (CSS) and overall survival (OS). Results: Lower levels of caspase-8 were more prevalent in patients with a higher T-stage (p = 0.002) and a higher FIGO stage (p = 0.003), and were significantly correlated with CDK9 expression (p = 0.018) and inversely with pCDK9 detection (p = 0.014). Increased caspase-8 levels corresponded to improved RFS (p = 0.005), DMFS (p = 0.038) and CSS (p = 0.017) in the univariate analyses. Low CDK9 expression was associated with worse RFS (p = 0.008), CSS (p = 0.015) and OS (p = 0.007), but not DMFS (p = 0.083), and remained a significant prognosticator for RFS (p = 0.003) and CSS (p = 0.009) in the multivariate analyses. Furthermore, low pCDK9 staining was significantly associated with superior RFS (p = 0.004) and DMFS (p = 0.001), and increased CSS (p = 0.022), and remained significant for these endpoints in the multivariate analyses. Conclusion: Increased caspase-8 and CDK9 levels correlate with improved disease-related outcomes in cervical cancer patients treated with CRT, whereas elevated pCDK9 levels predict worse survival in this patient population.

Long-term consequences of residual lesions after chemoradiotherapy in patients with germinoma at onset.

In patients with intracranial germ cell tumors, residual lesions are sometimes observed after completion of primary chemoradiotherapy. Although salvage resection of these end-of-treatment residual lesions is recommended for patients with nongerminomatous germ cell tumors, the necessity of early salvage resection for those with germinoma is not clear. The aim of this study was to investigate the frequency of residual germinoma lesions after primary chemoradiotherapy, as well as their management, long-term consequences, and prognosis. The authors retrospectively reviewed patients who were primarily treated for germinoma between 2002 and 2021. Residual lesions were evaluated with MRI with and without contrast enhancement within 2 weeks after chemoradiotherapy. The decision to perform salvage resection of residual lesions was at the discretion of the treating physicians. The change in appearance of residual lesions was assessed with serial MRI. Overall survival (OS), progression-free survival (PFS), and recurrence pattern were also investigated. Sixty-nine patients were treated with chemoradiotherapy for germinoma, with a mean follow-up period of 108 months. Residual lesions were radiologically observed in 30 patients (43.5%). Among these, 5 patients (3 with pineal lesions and 2 with basal ganglia lesions) underwent salvage resection. Pathological examination revealed teratomatous components in 3 patients, whereas no tumoral components were identified in 2 patients. One patient with a basal ganglia lesion showed worsening of hemiparesis postoperatively. The remaining 25 patients received watchful observation without surgical intervention. Chronological periodic radiological change in residual lesions was evaluated in 21 patients. One year after primary treatment, the size of the residual lesions was stable and had decreased in 10 and 11 patients, respectively. None of the lesions increased in size. The 10-year PFS and OS rates were 96.7% and 97.3% in patients without residual lesions (n = 39), and 87.1% and 100% in patients with residual lesions (n = 30), respectively. Presence of residual lesions had no significant effect on PFS or OS. All recurrences occurred at distant sites or via dissemination without progression of the primary tumor site, regardless of the presence of residual lesion. End-of-treatment residual lesions are not rare in patients with germinoma, and these residual lesions seldom show progression. Because of the potential risk of surgical complications, the indication for early salvage surgery for residual lesions should be carefully determined. Watchful observation is recommended for the majority of these cases.

The Choice of 2D-Brachytherapy or 3D-Brachytherapy for Cervical Cancer Patients after External Beam Radiation Based on Residual Gross Tumor Volume

<h3>Purpose/Objective(s)</h3> The purpose of this study was to analyze the choice of 2-dimensional brachytherapy (2D-BT) or 3-dimensional brachytherapy (3D-BT) for cervical cancer patients after external beam radiotherapy (EBRT), based on residual gross tumor volume (GTV res). <h3>Materials/Methods</h3> Between September 2019 and April 2020, 106 local advanced cervical cancer patients (FIGO stage IB3-IVA) who received primary radiation or chemoradiation followed by BT were analyzed retrospectively. We divided patients into large tumor group (GTV res > 30 mm³ or the width ≥ 4 cm) and small tumor group (GTV res ≤ 30 mm³). Point A and high-risk clinical target volume (CTV_HR) planning were designed for each patient; all patients received 4–5 fractions of intra-cavity BT with a single dose of 6 Gy. The CTV_HR, the bladder, and rectum were delineated, respectively, the D2cc (minimum dosage to the most irradiated 2 cc of an organ at risk) of bladder and rectum, D90 (dose to 90% of a target) of the target, vaginal dose point, and vaginal reference length (VRL) were compared. <h3>Results</h3> The patients who received BT fewer than 4 times (n = 2), had double primary tumors (n = 1), or had incomplete data (n = 3) were excluded. Thus, 106 patients were eligible and analyzed in this study. Of the 106 patients, 45 (42.5%) had an initial tumor size of > 4 cm before EBRT. After EBRT, 92 (86.8%) patients had small GTV res, the median of GTV res and CTV_HR were 2 cm³ and 17.85 cm³. The CTV_HR does not change with GTV res (r² = 0.16, <i>P</i> < 0.001), no matter the size of GTV res, both the point A dose and CTV_HR can satisfactorily reach the prescribed tumor coverage dose. However, when evaluated by volume dose, the CTV-_HR D90 was higher than the Point A dose; with reduced organs at risk (OARs) dose (bladder, rectum-, and vaginal dose point) (<i>P</i> < 0.05). The remainder of the patients had large GTV res, with a median of 64cm³, which is not covered by the Point A dose. While evaluated by volume dose, the median of CTV_HR was 71.6 cm³; as GTV res increased, the CTV_HR increased significantly (r² = 0.68, <i>P</i> < 0.001). The CTV_HR D90 to Point A dose ratio was negatively correlated with GTV res (r = -0.61, <i>P</i> < 0.001), and the Point A dose typically varied between 47% and 230% of the CTV_HR D90. In the OARs dose evaluation, only the vaginal dose points were lower in the CTV_HR plan. The 1-year and 2-year local controls for small and large tumor groups were 94.3% versus 78.6% and 91.9% versus 70.7%, respectively. <h3>Conclusion</h3> After EBRT, 86.8% of locally advanced cervical cancer (LACC) patients had small residual tumors, and 2D-BT can achieve adequate prescription dose coverage and meet treatment needs. Only 13.2% of patients had large residual tumors, and these patients should receive 3D-BT or treatment combined with interstitial needles to deliver a higher dose to the CTV_HR. To protect the OARs and reduce radiation damage in small resident tumor patients, 3D-BT would be the best choice.

Surgical Resection and Intensity Modulated Proton Therapy for Esthesioneuroblastoma

<h3>Purpose/Objective(s)</h3> Esthesioneuroblastoma (ENB) is a rare locally aggressive neuroendocrine sinonasal malignancy commonly presenting with skull base and intracranial invasion, which is often managed using multimodality therapy with surgery and radiotherapy (RT). Advances in surgical techniques as well as RT have improved outcomes for these complex tumors. Proton therapy has dosimetric advantages over conventional X-ray based approaches and may further improve the therapeutic ratio. We report our early experience with intensity modulated proton therapy (IMPT) in the management of ENB. <h3>Materials/Methods</h3> We retrospectively reviewed treatment records of patients with ENB treated at our center with IMPT from 2015-2021. IMPT was delivered with a 2 to 5 field pencil-beam scanning plan, initially with single-field optimization, then multi-field optimization after 2018. All pathology was internally reviewed. Event outcomes were calculated from date of biopsy to time of locoregional recurrence or death. Survival statistics were calculated using the Kaplan-Meier (KM) method using a scientific 2-D graphing and statistics software. <h3>Results</h3> 15 patients were identified, median age 52 (range 32-78), gender (male 12, female 3), Kadish stage (B – 2; C – 12; D – 1), AJCC T classification (T3 – 3, T4b – 12), 2 had nodal metastasis at diagnosis, Hyams (grade 2 – 10; grade 3-4 – 5). Local disease extent included: anterior cranial fossa – 11, middle cranial fossa – 2, dura – 12, brain parenchyma 1, nasopharynx – 2, orbit – 6. The majority (n=14) were managed with surgical resection followed by postoperative RT, and one underwent primary chemoradiation. Surgery included bifrontal craniotomy + extended endoscopic resection (n=7) and extended endoscopic resection alone (n=7). IMPT was delivered in conventional fractionation (n=12) or hyperfractionated accelerated course (n=3), median dose 68 CGE (range 60-72), neck coverage (n=11). Four received concurrent platinum-based chemotherapy. At median follow up of 20 months (IQR 16-51), 2 patients have died, unrelated to disease progression. Three patients have recurred including 1 local, 1 regional, and 1 distant metastasis (out of field dural metastases). Both patients with locoregional recurrence have undergone surgical salvage and have no evidence of disease. IMPT was well tolerated with expected acute toxicities. One patient developed frontal lobe brain necrosis at 3 years post-treatment managed conservatively, and one underwent functional sinus surgery for sinus obstruction. No de novo high grade visual toxicity was observed. KM 2-year locoregional recurrence-free survival was 83% and OS 88%. <h3>Conclusion</h3> IMPT is feasible in ENB with early outcomes demonstrating excellent local control and favorable toxicity profile in this cohort of patients with very locally advanced disease. IMPT may allow for improved coverage of tumor volumes in close proximity to numerous critical structures. Additional follow up is needed to track long term disease control outcomes and late toxicities.

The prognostic impact of PD-L1 and CD8 expression in anal cancer patients treated with chemoradiotherapy.

BackgroundProgrammed death-ligand 1 (PD-L1) expression has been shown to be prognostic in many cancer types and used in consideration of checkpoint inhibitor immunotherapy. However, there are very limited and conflicting data on the prognostic impact of PD-L1 in patients with anal squamous cell carcinoma (ASCC). The objectives of this study were to measure the expression of PD-L1 and CD8 in patients with ASCC treated with radical chemoradiotherapy (CRT) and to correlate tumor expression with progression-free survival (PFS) and overall survival (OS).MethodsNinety-nine patients with ASCC treated with primary CRT at two tertiary care cancer centers between 2000 and 2013, with available pre-treatment tumors, were included. Tissue microarrays (TMAs) from pre-treatment tumor specimens were stained for PD-L1 and CD8. PD-L1 expression in the tumor and stroma was quantified using HALO image analysis software, and results were interpreted using quantitative methods. The density of CD8 cells within the tumor was interpreted by a trained pathologist semi-quantitatively, using a 0-4 scoring system. Kaplan-Meier analysis with log-rank was used to determine the significance in the association of tumor markers with PFS and OS. Cox multivariate analysis was used to explore independent predictors of PFS and OS.ResultsOf the 99 patients, 63 (64%) had sufficient tumor samples available for full analysis. CD8 high status was documented in 32 of 63 (50.8%) % of cases. PD-L1 expression was positive in 88.9% of cases. Approximately half the patients had tumor PD-L1 ≥ 5%. Patients with tumor PD-L1 ≥ 5% had better OS vs those with lower expression, HR=0.32 (95% CI 0.11-0.87), p=0.027; 10 years OS: 84% for tumor PD-L1 ≥ 5% vs 49% for PD-L1 < 5%. PD-L1 expression was not associated with PFS. On multivariate analysis, tumor PD-L1 ≥ 5% showed a trend to statistical significance for better OS, HR=0.55 (95% CI 0.12- 1.00), p=0.052.ConclusionsTumor PD-L1≥5% is associated with OS in patients with ASCC treated with CRT. PD-L1 expression status using this unique cut-point warrants further validation for prognostication in patients with this disease. Future studies are required to determine the benefit of alternative treatment strategies based on PD-L1 status.

Integrated radiogenomics analyses allow for subtype classification and improved outcome prognosis of patients with locally advanced HNSCC

Patients with locally advanced head and neck squamous cell carcinoma (HNSCC) may benefit from personalised treatment, requiring biomarkers that characterize the tumour and predict treatment response. We integrate pre-treatment CT radiomics and whole-transcriptome data from a multicentre retrospective cohort of 206 patients with locally advanced HNSCC treated with primary radiochemotherapy to classify tumour molecular subtypes based on radiomics, develop surrogate radiomics signatures for gene-based signatures related to different biological tumour characteristics and evaluate the potential of combining radiomics features with full-transcriptome data for the prediction of loco-regional control (LRC). Using end-to-end machine-learning, we developed and validated a model to classify tumours of the atypical subtype (AUC [95% confidence interval] 0.69 [0.53–0.83]) based on CT imaging, observed that CT-based radiomics models have limited value as surrogates for six selected gene signatures (AUC < 0.60), and showed that combining a radiomics signature with a transcriptomics signature consisting of two metagenes representing the hedgehog pathway and E2F transcriptional targets improves the prognostic value for LRC compared to both individual sources (validation C-index [95% confidence interval], combined: 0.63 [0.55–0.73] vs radiomics: 0.60 [0.50–0.71] and transcriptomics: 0.59 [0.49–0.69]). These results underline the potential of multi-omics analyses to generate reliable biomarkers for future application in personalized oncology.

Preoperative prediction of retroperitoneal lymph node involvement in clinical stage IB and IIA cervical cancer.

Lymph node metastasis (LNM) is the most important factor affecting survival in early-stage cervical cancer (CC). International Federation of Gynecology and Obstetrics revised the staging of CC in 2018 and reported LNM as a staging criterion. We investigated the preoperatively assessable risk factors associated with LNM in surgically treated stage IB1-IIA2 CC patients. This was a retrospective cohort study of women who underwent radical hysterectomy and pelvic lymphadenectomy with or without para-aortic lymphadenectomy for CC stage IB1-IIA2 from 2004 to 2019. All patients included in this study were examined with speculum inspection, parametrial assessment by rectovaginal palpation under general anesthesia, transvaginal ultrasonography, magnetic resonance imaging (MRI), and chest radiography. Clinical staging was done according to the preoperative findings. MRI was used to measure tumor and lymph node dimensions. Out of the 149 women included in the study, 29 (19.4%) had LNM. Univariate analysis revealed that larger tumor size (≥30 mm), lymphovascular space invasion (LVSI) detected with diagnostic biopsy, parametrial involvement, and deep stromal invasion status were significantly different between the group with LNM and the group without LNM. In multivariate analysis, specific preoperative risk factors such as MRI based tumor diameter ≥30 mm and LVSI (+) on the diagnostic biopsy were found to be independent risk factors for LNM in the multivariate analysis. The rate of LNM is high in patients with CC with a tumor size ≥30 mm and preoperative biopsy LVSI status even if they are clinically in early stages. Surgeons can take this into account while deciding between primary surgery and chemoradiotherapy in the treatment of CC.

Primary concurrent chemoradiation therapy with triweekly cisplatin as a standard protocol in patients aged ≥65 years with head and neck squamous cell carcinoma.

To evaluate the results of primary concurrent chemoradiation therapy (CCRT) with triweekly cisplatin in patients with head and neck squamous cell carcinoma (HNSCC) aged ≥65 years by comparing these patients to those aged<65 years. This prospective, single-center study enrolled patients with HNSCC for whom CCRT was indicated as the primary treatment. The major endpoints were progression-free survival (PFS) and overall survival (OS). A total of 169 patients were enrolled; 75 (44.4%) and 94 (55.6%) patients were aged ≥65 and<65 years, respectively. The mean cumulative cisplatin doses were 192.8mg/m2 and 212.3mg/m2 in patients ≥65 and<65, respectively (p<.001). The incidence rates of any grade 3-4 toxicities were 37.3% and 51.1% in the age ≥65 and<65 groups, respectively (p=.085). The 5-year locoregional control, distant control, PFS, ultimate PFS, and disease-specific survival were comparable between both groups. The 5-year OS was significantly lower in the ≥65 group than the<65 group (65.5%vs. 86.4%, p=.010) due to a lower salvage rate and higher incidence of non-HNSCC-related death. In a Cox regression analysis, age ≥65 years was not associated with increased risk of treatment failure but was associated with higher overall death rate (hazard ratio, 2.590; 95% confidence interval, 1.219-5.502; p=.013). CCRT with a triweekly cisplatin regimen could act as the standard of ca for HNSCC in elderly patients. However, the relatively lower OS compared to younger patients should be acknowledged, despite a favorable disease control rates.

Oncological outcomes of cervical esophageal cancer treated primarily with surgery: a systematic review and meta-analysis.

To determine the oncological outcomes of cervical esophageal cancer (CEC) treated primarily with surgery. A systematic review and meta-analysis was performed according to the PRISMA guidelines. A total of 868 patients were included from 18 studies. Estimated pooled Overall Survival (OS) rates (95% Confidence Interval, CI) at 1 and 5years were 74.4% (66.5-83.3), and 26.6% (20.3-34.7), respectively. Larynx non-preserving surgery (n = 229) showed an estimated pooled OS rates (95% CI) at 1 and 5years of 59.3% (51.5-68.2) and 14.6% (8.8-24.3), respectively. On the other hand, larynx preserving surgery (n = 213) showed an estimated pooled OS rates (95% CI) at 1 and 5years of 83.6% (78.2-89.4) and 35.1% (24.9-49.6), respectively. Primary larynx-preserving surgery remains a valuable option for the management of CEC, with similar survival outcomes compared to primary chemoradiotherapy (CRT). On the other hand, larynx non-preserving surgery showed a significantly reduced survival, that may reflect the more advanced T classification of these tumors. Further studies are mandatory to directly compare primary surgery and primary CRT, distinguishing larynx preserving and non-preserving surgery.

EP-198 Is Primary surgical treatment of anal carcinoma safe and cost-effective in low resource settings?

Abstract Aims The aim of the study is to debate if primary surgical treatment (abdominoperineal (AP) resection remains safe and effective in low resource settings especially when considering the cost, availability, protracted treatment and complications of radiotherapy+/- chemotherapy. Methods An electronic literature search were performed to identify original published studies on anal carcinoma and management. Results The oncological outcome of primary surgical treatment is equivalent to chemoradiotherapy. The arguments for surgery as primary treatment are (1) Surgery is the primary treatment modality for small perianal lesions that can be locally excised, (2) a 55% 5-yr survival after a potentially curable AP resection of early locally advanced cancer, (3) 50% relapse after complete remission using chemoradiation and many can be salvaged by AP resection. (4) Four situations may require surgery after primary chemoradiotherapy (a) residual tumour, (b) complications of treatment, (c) incontinence or fistula after tumour resolution, (d) subsequent tumour recurrence. (5) Only a generous biopsy will reveal if a residual ulcer contains residual disease for which a salvage AP resection may be the only option as further radiotherapy cannot be given. (6) Salvage AP resection carries a high morbidity. The main arguments against surgery as primary treatment are the increased tumour radiosensitivity in the undisturbed pelvis with well oxygenated tissues and less small bowel in the radiation field limiting toxicity, (2) radiation therapy will reduce local recurrence better than after surgery (3) 20% are incurable surgically at presentation. Conclusions Primary surgical treatment of anal cancer may remain safe and cost-effective in low resource settings

Development and validation of prognostic models for anal cancer outcomes using distributed learning: protocol for the international multi-centre atomCAT2 study

BackgroundAnal cancer is a rare cancer with rising incidence. Despite the relatively good outcomes conferred by state-of-the-art chemoradiotherapy, further improving disease control and reducing toxicity has proven challenging. Developing and validating prognostic models using routinely collected data may provide new insights for treatment development and selection. However, due to the rarity of the cancer, it can be difficult to obtain sufficient data, especially from single centres, to develop and validate robust models. Moreover, multi-centre model development is hampered by ethical barriers and data protection regulations that often limit accessibility to patient data. Distributed (or federated) learning allows models to be developed using data from multiple centres without any individual-level patient data leaving the originating centre, therefore preserving patient data privacy. This work builds on the proof-of-concept three-centre atomCAT1 study and describes the protocol for the multi-centre atomCAT2 study, which aims to develop and validate robust prognostic models for three clinically important outcomes in anal cancer following chemoradiotherapy.MethodsThis is a retrospective multi-centre cohort study, investigating overall survival, locoregional control and freedom from distant metastasis after primary chemoradiotherapy for anal squamous cell carcinoma. Patient data will be extracted and organised at each participating radiotherapy centre (n = 18). Candidate prognostic factors have been identified through literature review and expert opinion. Summary statistics will be calculated and exchanged between centres prior to modelling. The primary analysis will involve developing and validating Cox proportional hazards models across centres for each outcome through distributed learning. Outcomes at specific timepoints of interest and factor effect estimates will be reported, allowing for outcome prediction for future patients.DiscussionThe atomCAT2 study will analyse one of the largest available cross-institutional cohorts of patients with anal cancer treated with chemoradiotherapy. The analysis aims to provide information on current international clinical practice outcomes and may aid the personalisation and design of future anal cancer clinical trials through contributing to a better understanding of patient risk stratification.

Pilot Cervical Cancer Navigation Program Outcomes from a Tertiary Tanzanian Academic Institute (037)

Pilot Cervical Cancer Navigation Program Outcomes from a Tertiary Tanzanian Academic Institute (037)

Oncologic outcomes of neoadjuvant chemotherapy followed by radical hysterectomy for locally advanced cervical cancer (311)

Objectives: To investigate the utilization and oncologic outcomes of neoadjuvant chemotherapy followed by radical hysterectomy for patients with locally advanced cervical cancer. Methods: Patients diagnosed between 2004-2015 with FIGO 2009 stage IB2-II squamous cell, adenocarcinoma, or adenosquamous cervical carcinoma with at least one month of follow-up with no history of another tumor were selected from the National Cancer Database. Patients who received neoadjuvant chemotherapy (defined as receipt of chemotherapy without radiation up to six months prior to surgery) followed by radical hysterectomy and those who received definitive chemoradiation (defined as external beam radiation therapy of at least 45 Gy, with same day concurrent chemotherapy and without adjuvant hysterectomy) were identified. Clinical-pathologic and demographic characteristics were compared. Overall survival (OS) was estimated following the generation of Kaplan-Meier curves and compared with the log-rank test. A Cox model was constructed to control for a priori selected confounders. Results: A total of 182 patients who received NACT followed by radical hysterectomy and 3859 patients who had definitive chemoradiation were identified. For patients who had a radical hysterectomy, the rate of positive margins was 7%, median hospital stay was 3 days and rate of unplanned re-admission within 30 days from discharge was 5.1% while most of them (90.1%) received adjuvant radiation, with 85 (46.7%) of them receiving brachytherapy. Compared to patients who received chemoradiation, those who had NACT/radical hysterectomy were younger (median 47 vs 50 years, p=0.001), and more likely to have stage IB2 disease (40.1% vs 23.2%, p<0.001) and adenocarcinoma (30.8% vs 13.9%, p<0.001). There was no difference in OS between the NACT/radical hysterectomy and chemoradiation groups (p=0.91); 5-year OS rates were 70.2% and 68.5%. There was no difference in OS for patients with stage IB2 (p=0.73) or stage II disease (p=0.39). After controlling for patient age, race, presence of comorbid conditions, tumor histology, and stage, NACT/radical hysterectomy was not associated with better OS (HR: 1.05, 95% CI: 0.80, 1.38). Conclusions: Neoadjuvant chemotherapy followed by radical hysterectomy is rarely utilized in the United States. Overall survival appears to be comparable to primary chemoradiation. Given no survival advantage and potentially increased morbidity, primary chemoradiation should remain the preferred treatment modality in a high- resource setting. Objectives: To investigate the utilization and oncologic outcomes of neoadjuvant chemotherapy followed by radical hysterectomy for patients with locally advanced cervical cancer. Methods: Patients diagnosed between 2004-2015 with FIGO 2009 stage IB2-II squamous cell, adenocarcinoma, or adenosquamous cervical carcinoma with at least one month of follow-up with no history of another tumor were selected from the National Cancer Database. Patients who received neoadjuvant chemotherapy (defined as receipt of chemotherapy without radiation up to six months prior to surgery) followed by radical hysterectomy and those who received definitive chemoradiation (defined as external beam radiation therapy of at least 45 Gy, with same day concurrent chemotherapy and without adjuvant hysterectomy) were identified. Clinical-pathologic and demographic characteristics were compared. Overall survival (OS) was estimated following the generation of Kaplan-Meier curves and compared with the log-rank test. A Cox model was constructed to control for a priori selected confounders. Results: A total of 182 patients who received NACT followed by radical hysterectomy and 3859 patients who had definitive chemoradiation were identified. For patients who had a radical hysterectomy, the rate of positive margins was 7%, median hospital stay was 3 days and rate of unplanned re-admission within 30 days from discharge was 5.1% while most of them (90.1%) received adjuvant radiation, with 85 (46.7%) of them receiving brachytherapy. Compared to patients who received chemoradiation, those who had NACT/radical hysterectomy were younger (median 47 vs 50 years, p=0.001), and more likely to have stage IB2 disease (40.1% vs 23.2%, p<0.001) and adenocarcinoma (30.8% vs 13.9%, p<0.001). There was no difference in OS between the NACT/radical hysterectomy and chemoradiation groups (p=0.91); 5-year OS rates were 70.2% and 68.5%. There was no difference in OS for patients with stage IB2 (p=0.73) or stage II disease (p=0.39). After controlling for patient age, race, presence of comorbid conditions, tumor histology, and stage, NACT/radical hysterectomy was not associated with better OS (HR: 1.05, 95% CI: 0.80, 1.38). Conclusions: Neoadjuvant chemotherapy followed by radical hysterectomy is rarely utilized in the United States. Overall survival appears to be comparable to primary chemoradiation. Given no survival advantage and potentially increased morbidity, primary chemoradiation should remain the preferred treatment modality in a high- resource setting.

Oncologic outcomes of pelvic exenteration for stage IVA cervical cancer: A rarely utilized treatment modality (528)

<b>Objectives:</b> To investigate the outcomes of pelvic exenteration for patients with FIGO stage IVA cervical carcinoma. <b>Methods:</b> Patients diagnosed between 2004 and 2015 with FIGO 2009 stage IVA squamous cell, adenocarcinoma, or adenosquamous cervical carcinoma with no history of another tumor were selected from the National Cancer Database. Patients who received definitive chemoradiation (defined as external beam radiation therapy of at least 45 Gy, with concurrent chemotherapy) with no other surgical procedure and those who underwent primary pelvic exenteration with negative surgical margins were identified. Clinical-pathologic and demographic characteristics were compared. Overall survival was compared following 1:1 propensity score matching for the year of diagnosis, patient age, comorbid conditions, patient race, and insurance status. <b>Results:</b> A total of 64 patients who underwent pelvic exenteration and had negative margins were identified. The comparison group included 1176 patients who had definitive chemoradiation and did not undergo any surgical procedure. There was no statistically significant difference between the two groups in terms of patient age, race, and presence of comorbid conditions. However, patients who underwent exenteration were more likely to have private insurance (59.4% vs 34.4%, p<0.001). For patients who underwent exenteration, the unplanned re-admission rate was 11.5%, while median hospital stay was 11.5 days and 90-day mortality was 3.3%. The majority also received radiation therapy (85.9%). Following propensity score matching, patients who underwent pelvic exenteration had better OS (5-yr OS rate: 48.1%, median OS: 43.96 months) compared to those who had chemoradiation (5-yr OS rate: 16.5%, median OS: 18.63 months). <b>Conclusions:</b> Pelvic exenteration is rarely utilized in the management of patients with stage IVA cervical cancer. For carefully selected patients, overall survival may be superior to primary chemoradiation.

Comparison of Dosimetric Parameters in Dysphagia Aspiration-Related Structures and Clinical Correlation in Head and Neck Cancer Patients Treated With Radiotherapy.

IntroductionChemoradiotherapy plays a major role in the treatment of head and neck cancer (HNC). Persistent dysphagia following primary chemoradiotherapy for head and neck cancers can have a devastating effect on a patient’s quality of life. Many studies have shown that the dosimetric sparing of critical structures which were included in swallowing such as the pharyngeal constrictor muscle and larynx can provide improved functional outcomes and better quality of life. However, there are no current randomized studies confirming the benefits of such swallowing-sparing strategies. The aim is to evaluate late dysphagia after chemoradiotherapy for head and neck cancer and to examine its correlation with clinical and dosimetric parameters.Materials and methodsThe period of this prospective study was from November 2018 to March 2020. Patients were divided randomly in 1:1 ratio into two groups, group 1 and group 2, each with 25 patients. Group 1 was planned by three-dimensional conformal radiotherapy (3D-CRT) technique and group 2 was planned by intensity-modulated radiotherapy technique (IMRT) technique. Treatment was delivered after approval of radiotherapy plan. To evaluate the dose to dysphagia aspiration-related structures (DARS), these structures were contoured and dose-volume histograms were generated. Various dosimetric parameters of DARS were evaluated. Swallowing status was clinically evaluated based on the Radiation Therapy Oncology Group and the Common Terminology Criteria for Adverse Events, version 5.ResultsA significant advantage was seen with intensity-modulated radiotherapy technique (IMRT) in comparison to three-dimensional conformal radiotherapy (3D-CRT) in terms of mean dose delivered to the pharyngeal constrictor muscles (66.03 Gy vs 68.77 Gy, p=0.003). The mean dose delivered to the combined dysphagia/aspiration-related structures (DARS) was statistically significantly lower in IMRT compared to 3D-CRT (66.15 Gy vs. 70.09 Gy, p<0.001). Other dose-volumes were also reduced in IMRT group (V30: {98.64% vs. 99.88%, p=0.05}; V50: {90.49% vs. 99.02%, p=0.0002}; V60: {83.92% vs. 95.04, p=0.0002}; D50: {70 Gy vs. 71.16 Gy, p=0.001); and D80: {61.18 Gy vs. 67.39 Gy, p=0.01}. Futhermore, the clinical worsening of dysphagia was less common in IMRT group (48% vs. 80%, p=0.039).ConclusionIMRT can reduce the high-dose volumes received by the DARS receiving high doses by sparing these structures through optimization. This may provide a significant additional benefit that could improve dysphagia and hence the quality of life of patients with head and neck cancer.