Development and Validation of Single-Optimization Knowledge-Based Volumetric Modulated Arc Therapy Model Plan in Nasopharyngeal Carcinomas.

Purpose: Knowledge-based planning (KBP) has evolved to standardize and expedite the complex process of radiation therapy planning for nasopharyngeal cancer (NPC). Herein, we aim to develop and validate the suitability of a single-optimization KBP for NPC. Methods and Materials: Volumetric modulated arc therapy plans of 103 patients with NPC treated between 2016 and 2020 were reviewed and used to generate a KBP model. A validation set of 15 patients was employed to compare the quality of single optimization KBP and clinical plans using the paired t test and the Wilcoxon signed rank test. The time required for either planning was also analyzed. Results: Most patients (86.7%) were of locally advanced stage (III/IV). The median dose received by 95% of the high-risk planning target volume was significantly higher for the KBP (97.1% vs 96.4%; P = .017). The median homogeneity (0.09 vs 0.1) and conformity (0.98 vs 0.97) indices for high-risk planning target volume and sparing of the normal tissues like optic structures, spinal cord, and uninvolved dysphagia and aspiration-related structures were better with the KBP (P < .05). In the blinded evaluation, the physician preferred the KBP plan in 13 out of 15 patients. The median time required to generate the KBP and manual plans was 53 and 77 minutes, respectively. Conclusions: KBP with a single optimization is an efficient and time saving alternative for manual planning in NPC.

Intensity-Modulated Radiation Therapy Alone Versus Intensity-Modulated Radiation Therapy and Brachytherapy for Early-Stage Oropharyngeal Cancers: Results From a Randomized Controlled Trial.

PURPOSE: The objective of this study was to compare clinical outcomes of intensity-modulated radiation therapy (IMRT) alone versus IMRT + brachytherapy (BT) in patients with T1-T2N0M0 oropharyngeal squamous cell cancers (OPSCC). METHODS AND MATERIALS: This open-label randomized controlled trial was conducted at Tata Memorial Hospital, Mumbai, India. Patients with stage I and II OPSCC were considered for IMRT to a dose of 50 Gy/25 fractions/5 weeks in phase I followed by randomization (1:1) to further treatment with IMRT (20 Gy/10 fractions/2 weeks) or BT (192Ir high dose rate, 21 Gy/7 fractions/2 fractions per day). The primary endpoint of the trial was the reduction in xerostomia at 6 months evaluated using 99mTc salivary scintigraphy. Severe salivary toxicity (xerostomia) was defined as posttreatment salivary excretion fraction ratio <45%. Secondary endpoints were local control, disease-free survival, and overall survival. RESULTS: Between November 2010 and February 2020, 90 patients were randomized to IMRT (n = 46) alone or IMRT + BT (n = 44). Eleven patients (8 residual/recurrent disease, 2 lost to follow-up, 1 second primary) in the IMRT arm and 9 patients (8 residual/recurrence, 1 lost to follow-up) in the BT arm were not evaluable at 6 months for the primary endpoint. At 6 months, xerostomia rates using salivary scintigraphy were 14% (5/35: 95% CI, 5%-30%) in the BT arm while it was seen in 44% (14/32: 95% CI, 26%-62%) in the IMRT arm (P = .008). Physician-rated Radiation Therapy Oncology Group grade ≥2 xerostomia at any time point was observed in 30% of patients (9/30) in the IMRT arm and 6.7% (2/30) in the BT arm (P = .02). At a median follow-up of 42.5 months, the 3-year local control in the IMRT arm was 56.4% (95% CI, 43%-73%) while it was 66.2% (95% CI, 53%-82%) in the BT arm (P = .24). CONCLUSIONS: The addition of BT to IMRT for T1-T2N0M0 OPSCC results in a significant reduction in xerostomia. This strongly supports the addition of BT to IMRT in suitable cases.

Diagnostic Performance of Response Assessment FDG-PET/CECT in HNSCC Treated With Definitive Radio(chemo)therapy Using NI-RADS.

OBJECTIVE: To assess the diagnostic performance of response assessment 18F-fluorodeoxyglucose positron emission tomography/contrast-enhanced computed tomography (FDG-PET/CECT) following definitive radio(chemo)therapy in head and neck squamous cell carcinoma (HNSCC) using Neck Imaging Reporting and Data System (NI-RADS). STUDY DESIGN: A retrospective analysis from a prospectively maintained dataset. SETTING: Tertiary-care comprehensive cancer center in a low-middle-income country. METHODS: Adults with newly diagnosed, biopsy-proven, nonmetastatic HNSCC treated with definitive radio(chemo)therapy were included. Posttreatment response assessment FDG-PET/CECT scans were retrospectively assigned NI-RADS categories (1-3) for the primary site, neck, and both sites combined. Locoregional recurrence occurring within 2-years was defined as the event of interest. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall accuracy were calculated. Locoregional control stratified by NI-RADS categories was computed with the Kaplan-Meier method and compared using the log-rank test. RESULTS: Posttreatment FDG-PET/CECT scans were available in 190 patients constituting the present study cohort. Sensitivity, specificity, PPV, NPV, and overall accuracy of the NI-RADS template for the primary site was 73.5%, 81.4%, 46.3%, 93.4%, and 80.0%, respectively. Similar metrics for the neck were 72.7%, 87.5%, 43.2%, 96.1%, and 85.8%, respectively. Combining primary site and neck, the corresponding metrics of diagnostic accuracy were 84.4%, 69.7%, 46.3%, 93.5%, and 73.2%, respectively. At a median follow-up of 40 months, Kaplan-Meier estimates of 2-year locoregional control were significantly higher for NI-RADS category 1 (94.2%) compared to NI-RADS category 2 (69.4%) and category 3 (20.4%), respectively (stratified log-rank p < .0001). CONCLUSION: FDG-PET/CECT using the NI-RADS template is associated with good diagnostic performance and prognostic utility in HNSCC treated with definitive radio(chemo)therapy.

Prophylactic versus reactive feeding approach in patients undergoing adjuvant radiation therapy for oral cavity squamous cell carcinoma: A propensity score matched-pair analysis.

BACKGROUND: To assess the efficacy of prophylactic versus reactive feeding strategy in oral cavity squamous cell carcinoma (OCSCC) patients receiving adjuvant radiation therapy (RT). METHODS: This was a post hoc analysis of patients of OCSCC enrolled in a randomized trial comparing three adjuvant strategies. In this trial, till 2010, a prophylactic feeding approach was followed for all patients. Since January 2011, a reactive feeding approach was followed. RESULTS: Two hundred and sixty-eight in each cohort (total n = 526) were eligible for analysis after propensity score matching. At 6 weeks post-RT completion, the median weight loss in the prophylactic versus reactive cohort was 5 versus 3 kg, p = 0.002. At all other time points until 1 year, the median weight loss was lesser in reactive than in the prophylactic cohort. CONCLUSIONS: A reactive feeding tube approach should be preferred for OCSCC receiving adjuvant RT.

Oral cavity adjuvant therapy (OCAT) -a phase III, randomized controlled trial of surgery followed by conventional RT (5 fr/wk) versus concurrent CT-RT versus accelerated RT (6fr/wk) in locally advanced, resectable, squamous cell carcinoma of oral cavity.

BACKGROUND: Limited data exists regarding the impact of intensification of adjuvant therapy in resected Oral Cavity Squamous Cell Carcinomas (OCSCC) with adverse prognostic features on histopathology. PATIENTS AND METHODS: This was a three-arm phase III, randomised trial including patients with resected advanced OCSCC. Randomisation was done in a 1:1:1 ratio: Arm-A- standard adjuvant radiation therapy (RT) 60Gy/30 fractions over 6 weeks versus Arm-B-concurrent chemoradiation versus Arm-C-accelerated radiation therapy (6 d a week). The trial was powered to detect an absolute difference of 10% in 5-year Locoregional Control (LRC). RESULTS: The trial was conducted between June 2005 and March 2013. Majority of the patients were males, had T3-T4 disease, had N2-N3 nodal status and had Extra-Capsular Extension (ECE) in nodes. The median follow-up was 95.9 months. There was no difference between the three arms (A versus B versus C) for 10-year locoregional control (LRC): 60.2% versus 61.4% versus 65.7%, p = 0.57; disease free survival (DFS): 37.4% versus 43.9% versus 39.6%, p = 0.40; or Overall Survival (OS): 39.7% versus 46.6% versus 40.4%, p = 0.40. There was no benefit of intensification with either modality in patients with any single adverse pathological factor. A benefit of intensification could be seen in patients with a combination of high-risk features: T3-T4 primary tumours with N2-N3 nodes along with ECE for DFS (Arm B versus Arm A HR) = 0.53, Arm C versus Arm A HR = 0.63) and OS (Arm B versus Arm A HR = 0.58, Arm C versus Arm A HR = 0.60). CONCLUSIONS: All optimally resected OCSCC with adverse features did not benefit from intensification of adjuvant therapy. Only a cohort of patients with a combination of high-risk features are likely candidates for intensification. CLINICAL TRIAL REGISTRATION: NCT00193843.

Results of Phase III Randomized Trial for Use of Docetaxel as a Radiosensitizer in Patients With Head and Neck Cancer, Unsuitable for Cisplatin-Based Chemoradiation.

PURPOSE: There is a lack of published literature on systemic therapeutic options in cisplatin-ineligible patients with locally advanced head and neck squamous cell carcinoma (LAHNSCC) undergoing chemoradiation. Docetaxel was assessed as a radiosensitizer in this situation. METHODS: This was a randomized phase II/III study. Adult patients (age ≥ 18 years) with LAHNSCC planned for chemoradiation and an Eastern Cooperative Oncology Group performance status of 0-2 and who were cisplatin-ineligible were randomly assigned in 1:1 to either radiation alone or radiation with concurrent docetaxel 15 mg/m2 once weekly for a maximum of seven cycles. The primary end point was 2-year disease-free survival (DFS). RESULTS: The study recruited 356 patients between July 2017 and May 2021. The 2-year DFS was 30.3% (95% CI, 23.6 to 37.4) versus 42% (95% CI, 34.6 to 49.2) in the RT and Docetaxel-RT arms, respectively (hazard ratio, 0.673; 95% CI, 0.521 to 0.868; P value = .002). The corresponding median overall survival (OS) was 15.3 months (95% CI, 13.1 to 22.0) and 25.5 months (95% CI, 17.6 to 32.5), respectively (log-rank P value = .035). The 2-year OS was 41.7% (95% CI, 34.1 to 49.1) versus 50.8% (95% CI, 43.1 to 58.1) in the RT and Docetaxel-RT arms, respectively (hazard ratio, 0.747; 95% CI, 0.569 to 0.980; P value = .035). There was a higher incidence of grade 3 or above mucositis (22.2% v 49.7%; P < .001), odynophagia (33.5% v 52.5%; P < .001), and dysphagia (33% v 49.7%; P = .002) with the addition of docetaxel. CONCLUSION: The addition of docetaxel to radiation improved DFS and OS in cisplatin-ineligible patients with LAHNSCC.[Media: see text].

Image-guidance triggered adaptive radiation therapy in head and neck squamous cell carcinoma: single-institution experience and implications for clinical practice.

PURPOSE: To report frequency and timing of adaptive radiotherapy (ART) and assess patient, disease, and treatment-related characteristics potentially triggering the need for such adaptive replanning in head and neck squamous cell carcinoma (HNSCC). METHODS: Medical records of HNSCC patients treated with definitive intensity modulated radiation therapy (IMRT) with or without concurrent systemic chemotherapy were reviewed retrospectively to identify patients undergoing image-guidance triggered adaptive replanning. Clinico-demographic characteristics of patients undergoing ART were compared with patients treated without adaptation using the chi-square test. RESULTS: Two hundred patients with squamous cell cancers of the oropharynx, larynx, or hypopharynx treated with definitive IMRT between 2014 to 2019 comprised the study cohort. Twenty-seven (13.5%) patients underwent adaptive replanning during treatment at a median of 17 fractions (inter-quartile range 14-24 fractions). There were no significant differences in the baseline patient (age, gender), disease (site of primary, staging/grouping), and treatment-related characteristics (dose-fractionation, chemotherapy usage) in patients undergoing ART compared to those treated without adaptation. Weight loss during IMRT emerged as a significant factor predicting the need for ART; patients having ≥10% weight loss from baseline were more likely to undergo treatment adaptation compared to patients with <10% weight loss (p = 0.0002). There was variable impact of ART on dose-volume statistics of organs-at-risk such parotid glands and spinal cord. CONCLUSION: Image-guidance triggered ART for HNSCC is not associated with significant improvement in OAR dosimetry. However, weight loss during definitive IMRT can be a potentially useful trigger for identifying patients who are most likely to benefit from such adaptive replanning.

Definitive and adjuvant radiation therapy for external auditory canal and temporal bone squamous cell carcinomas: Long term outcomes.

INTRODUCTION: Primary Squamous Cell Carcinoma (SCC) of the external auditory canal (EAC) and Temporal Bone (TB) are rare entities with very few large reports on outcomes and toxicities. MATERIALS AND METHODS: A retrospective audit of all SCC of EAC/TB tumors treated with curative intent RT at our Institute between January 2007 and December 2019 was undertaken. The primary endpoint of the study was event-free survival (EFS). RESULTS: Eighty-nine patients were eligible for analysis. The median age was 54 years. The median follow-up of surviving patients was 61 months. Sixty-five patients received adjuvant RT, and 24 received definitive RT. Neoadjuvant Chemotherapy for aiding resectability was used in 12 patients, out of which 8 underwent surgery. The 5-year LRC, EFS, and OS were 66.2%, 57.8%, and 63.5%. The predominant pattern of failure was local (n = 36, 40.4%). Regional failure was seen in only five patients, none of which were in patients in whom elective nodal irradiation had been omitted post-operatively. On multivariable analysis adjuvant RT was associated with superior outcomes than definitive RT. Treatment with IMRT resulted in lower ≥ grade 2 late subcutaneous fibrosis (8.7% vs. 38.1%) compared to conventional/3D-CRT technique. CONCLUSIONS: Surgery followed by adjuvant therapy should remain the mainstay of treatment for EAC and TB SCC. IMRT should be the preferred modality for RT due to lower late morbidity. Elective nodal irradiation is routinely not warranted in the adjuvant setting for EAC and TB squamous cell carcinomas.

Stereotactic body radiotherapy (SBRT) for primary non-metastatic head and neck cancer: When less is enough.

The advantage of highly conformal dose distribution and steep dose gradient has resulted in rapidly increasing use of stereotactic body radiotherapy (SBRT) in multiple cancer sites. Also there has been a surge in the use of SBRT in head neck cancer over the last decade. It is predominantly exploited in retreatment setting for recurrent and second primary head neck cancer as well as in metastatic setting. The literature on SBRT in primary non-metastatic head neck cancer is sparse and evolving. In the current review, available literature was critically analyzed focusing on the potential applications of SBRT in primary untreated non-metastatic head neck cancer. SBRT boost following external beam radiotherapy is temping as a method of dose escalation. Special attention was paid to the application of SBRT as a sole modality of treatment. The shorter treatment schedule makes it an attractive option for treatment in primary head neck cancer especially in elderly, co-morbid and medically unfits patients. Future investigation is needed to establish SBRT as an additional armamentarium in the radiotherapeutic management of head and neck cancers.

Intensity-modulated radiation therapy for nasal cavity and paranasal sinus tumors: Experience from a single institute.

BACKGROUND: To assess the efficacy of intensity-modulated radiation therapy (IMRT) for tumors of the nasal cavity and paranasal sinus (PNS) region. MATERIALS AND METHODS: Two hundred fourteen patients with tumors of the nasal cavity and PNS region treated with curative intent IMRT between 2007 and 2019 were included in this retrospective analysis. RESULTS: Fifty-one (24.1%) received definitive RT/CTRT and 163 (75.9%) received adjuvant RT. Most common histology was squamous cell carcinoma (26.1%) followed by adenoid cystic carcinoma (21.5%). The median follow-up was 43.5 months. The 5-year local control (LC), event-free survival (EFS), and overall survival (OS) for the entire cohort was 66.9%, 59%, and 73.9%, respectively. On univariate analysis treatment with nonsurgical modality, T classification and undifferentiated/poorly differentiated histology were associated with inferior 5-year LC, EFS, and OS. Four patients had late Grade 3/Grade 4 ocular toxicity. CONCLUSIONS: IMRT should be the standard of care for tumors of PNS region across all histologies and treatment setting.

Concurrent chemoradiotherapy for locally advanced unresectable adenoid cystic carcinoma of head and neck: experience from a single institute.

PURPOSE: To analyze the outcome of locally advanced unresectable adenoid cystic carcinoma (ACC) of head and neck treated with radical concurrent chemoradiotherapy (CRT) at a single tertiary care centre. METHODS: Between 2011 and 2018, 23 patients with locally advanced unresectable ACC of head and neck treated with non-surgical radical treatment with concurrent chemoradiotherapy were evaluated for outcome and toxicity. All but one patient received cisplatin-based concurrent chemotherapy and 74% of patients were treated with intensity-modulated radiotherapy. RESULTS: Median follow-up was 53 months (range 3-115 months). Following treatment, 11 patients achieved complete response (47.8%) and of the 12 patients with residual disease, 7 patients additionally had disease stabilization without local progression. Overall 15 patients had disease progression. Median time to progression was 28 months (range 6-67 months). The 3-year and 5-year overall survival, local progression-free survival (LPFS) and distant progression-free survival (DPFS) were 78%, 79.7%, 67.4% and 63%, 50.9%, 48.6%, respectively. Acute grade 3 mucositis was observed in three patients, and one patient additionally developed grade 4 neutropenia with subsequent complete recovery. No grade 3 or higher late toxicity was observed. CONCLUSION: Radical concurrent chemoradiotherapy is a promising treatment option in locally advanced unresectable ACC with acceptable toxicity.

Implications of limited exolaryngeal disease and cricoarytenoid joint involvement in organ conservation protocols for laryngopharyngeal cancers: Results from a prospective study.

BACKGROUND: To identify clinicoradiological factors that determine functional outcomes in laryngopharyngeal cancers treated with chemoradiotherapy. METHODS: One hundred patients of locally advanced laryngopharyngeal cancers who were treated with chemoradiotherapy were accrued in this prospective study. The coprimary endpoint of the study was local control (LC) and functional larynx preservation survival (FLPS). RESULTS: The median follow-up was 39 months. Thirty-nine patients had a local failure of which 17 underwent a salvage laryngectomy. A dysfunctional larynx with clinic-radiologically disease was seen in only 1 patient. Factors significant for LC were thyroid cartilage erosion/lysis and cricoarytenoid joint involvement. Within the T4a subset, patients with exolaryngeal disease through the soft tissue framework had significantly better LC and FLPS than those with cartilage erosion/lysis. CONCLUSIONS: Patients with limited exolaryngeal disease through the soft-tissue framework can be considered for functional organ preservation, while those with thyroid cartilage involvement and cricoarytenoid joint involvement are not suitable.

Intensity-modulated radiation therapy versus three-dimensional conformal radiotherapy in head and neck squamous cell carcinoma: long-term and mature outcomes of a prospective randomized trial.

PURPOSE: To compare long-term disease-related outcomes and late radiation morbidity between intensity-modulated radiation therapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT) in head and neck squamous cell carcinoma (HNSCC) in the setting of a prospective randomized controlled trial. METHODS: Previously untreated patients with early to moderately advanced non-metastatic squamous carcinoma of the oropharynx, larynx, or hypopharynx (T1-T3, N0-N2b, M0) planned for comprehensive irradiation of primary site and bilateral neck nodes were randomly assigned to either IMRT or 3D-CRT after written informed consent. Patients were treated with 6MV photons to a total dose of 70Gy/35 fractions over 7 weeks (3D-CRT) or 66Gy/30 fractions over 6 weeks (IMRT). A sample size of 60 patients was estimated to demonstrate 35% absolute difference in the incidence of ≥grade 2 acute xerostomia between the two arms. All time-to-event outcomes were calculated from date of randomization until the defined event using the Kaplan-Meier method. RESULTS: At a median follow-up of 140 months for surviving patients, 10-year Kaplan-Meier estimates of loco-regional control (LRC); progression-free survival (PFS); and overall survival (OS) with 95% confidence interval (95%CI) were 73.6% (95%CI: 61.2-86%); 45.2% (95%CI: 32-58.4%); and 50.3% (95%CI: 37.1-63.5%) respectively. There were no significant differences in 10-year disease-related outcomes between 3D-CRT and IMRT for LRC [79.2% (95%CI: 62.2-96.2%) vs 68.7% (95%CI: 51.1-86.3%), p = 0.39]; PFS [41.3% (95%CI: 22.3-60.3%) vs 48.6% (95%CI: 30.6-66.6%), p = 0.59]; or OS [44.9% (95%CI: 25.7-64.1%) vs 55.0% (95%CI: 37-73%), p = 0.49]. Significantly lesser proportion of patients in the IMRT arm experienced ≥grade 2 late xerostomia and subcutaneous fibrosis at all time-points. However, at longer follow-up, fewer patients remained evaluable for late radiation toxicity reducing statistical power and precision. CONCLUSIONS: IMRT provides a clinically meaningful and sustained reduction in the incidence of moderate to severe xerostomia and subcutaneous fibrosis compared to 3D-CRT without compromising disease-related outcomes in long-term survivors of non-nasopharyngeal HNSCC.

Clinical outcomes for nasopharyngeal cancer with intracranial extension after taxane-based induction chemotherapy and concurrent chemo-radiotherapy in the modern era.

OBJECTIVE: To evaluate the survival outcomes for a cohort of nasopharyngeal cancer with intracranial extension (ICE) treated with induction chemotherapy (ICT) followed by chemo-intensity-modulated radiotherapy (CTRT) at a tertiary cancer center. METHODS: We retrospectively analyzed 45 patients with histologically proven, non-metastatic NPC with ICE treated at our institute between October 2008 and October 2016. Patients were classified as minor ICE or major ICE, based on the extent of ICE. All the patients received 2-3 cycles of a taxane-based ICT regimen followed by CTRT. Radiotherapy was delivered with "risk-adapted" intensity-modulated radiotherapy (IMRT) technique in all patients. RESULTS: After a median follow up of 45 months (range: 8-113 months), the estimated 5-year DFS, LRFS, DMFS, and OS of the entire cohort was 58%, 82%, 67% and 74% respectively. On multivariate analysis, histological subtype was an independent predictor of LRFS, and age was an independent predictor of DFS. The extent of ICE showed only a trend towards worse DFS (P = 0.06). None of the factors significantly predicted for DMFS or OS. Gender, N-stage, and response to ICT did not significantly affect any of the outcomes. Grade 2 or worse subcutaneous fibrosis was seen in 22% of patients and grade 2 or worse xerostomia was seen in 24% of patients at last follow up. Thirty-three percent of the patients developed clinical hypothyroidism at last follow up. None of the patients experienced any neurological or vascular complications. CONCLUSIONS: Taxane-based induction chemotherapy followed by chemo-intensity modulated radiotherapy resulted in excellent locoregional control and survival with acceptable toxicities in patients of nasopharyngeal cancer with intracranial extension. Distant metastasis continues to be the predominant problem in these patients.

Patterns of Recurrence and Predictors of Survival in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy, Surgery, and Radiation.

PURPOSE: Neoadjuvant chemotherapy (NAC) is standard of care for locally advanced breast cancer. There is wide variation in radiation therapy (RT) practice and limited data describing locoregional relapse (LRR) after NAC. We hypothesized a low LRR risk with modern NAC, surgery, and RT and aimed to elucidate patterns of LRR and predictors of disease-free survival (DFS) and overall survival (OS) in these patients. METHODS AND MATERIALS: Data from 416 patients with stage II/III breast cancer treated between 2008 and 2015 with NAC, surgery, and adjuvant RT were reviewed retrospectively. DFS and OS rates were calculated using the Kaplan-Meier method. The LRR rate was estimated using the cumulative incidence function, treating death as a competing risk. Multivariable survival analysis was performed using Cox regression. RESULTS: Median follow-up was 4.7 years. Most patients had cT2/3 (74%) cN1 (61%) disease and underwent mastectomy (75%) and axillary dissection (84%). Pathologic complete response (pCR) was achieved in 22% of patients. There were 27 LRRs (including 4 isolated LRRs) and 89 distant failures. Two patients developed LRR 2 months after surgery, before adjuvant RT. LRR could be mapped in 23 patients: most (20) recurred within the RT field; 1 in- and out-of-field; and 2 out-of-field. Five-year LRR, DFS, and OS were 6.4%, 77%, and 90%, respectively. On multivariable analysis, triple-negative subtype (hazard ratio [HR] 2.82; 95% confidence interval [CI], 1.78-4.47; P < .001), stage III disease (HR 1.72; 95% CI, 1.11-2.69; P = .016), and non-pCR (HR 4.76; 95% CI 2.13-10.0; P < .001) were associated with poor DFS and OS (HR 4.13 [95% CI, 2.21-7.72; P < .001]; HR 1.94 [95% CI, 1.001-3.75; P = .049]; and HR 2.38 [95% CI, 0.98-5.88; P = .055], respectively). CONCLUSIONS: Patients with breast cancer treated with modern NAC, surgery, and RT have a low 5-year LRR risk, with the majority occurring in-field. Triple-negative subtype, stage III disease, and non-pCR were associated with inferior DFS and OS.

Meningioma Screening With MRI in Childhood Leukemia Survivors Treated With Cranial Radiation.

PURPOSE: Radiation-induced meningioma is a known late effect of cranial radiation therapy. Cranial magnetic resonance imaging (MRI) can detect small meningiomas, but its potential value as a screening tool is unknown. METHODS AND MATERIALS: MRI was used to screen asymptomatic survivors of childhood acute lymphoblastic leukemia (ALL) treated with cranial radiation therapy ≥10 years previously. The incidence of radiation-induced meningioma and outcomes of this group were compared with a historical cohort of survivors with the same exposure who underwent imaging only to investigate clinical signs or symptoms. RESULTS: One hundred seventy-six childhood leukemia survivors were included in this study: 70 in the screening group and 106 unscreened. Screening MRI was performed a median of 25 years after radiation therapy and detected meningioma in 15 (21.4%). In the unscreened group, 17 patients (16.0%) had neurologic symptoms leading to an MRI a median interval of 24 years after radiation therapy, 9 of whom (8.5%) were diagnosed with meningioma. There was no significant difference between screened versus unscreened patients in the size of meningioma (mean diameter, 1.6 cm vs 2.6 cm; P = .13), meningioma incidence (7.4% vs 4.0% at 25 years; P = .19), or extent of resection. Three patients had persistent neurologic symptoms in the unscreened group versus none among screened patients (P = .28). CONCLUSIONS: Screening MRI was able to detect small meningiomas that were not clinically apparent; however, we could not demonstrate a significant improvement in the chance of total resection or a significant decrease in morbidity. A larger sample could clarify potential reduction in neurologic sequelae associated with screening.

Extranodal extension in resected oral cavity squamous cell carcinoma: more to it than meets the eye.

OBJECTIVE/HYPOTHESIS: Extranodal extension (ENE) is an independent prognosticator in head-neck Squamous cell carcinoma (SCC). All patients with ENE, however, do not behave the same, and there is a need for further risk stratification. This study evaluates the prognostic significance of various grades of ENE and the number of nodes with ENE on overall survival (OS) in oral cavity SCC (OCSCC). STUDY DESIGN: Retrospective cohort study. METHODS: Ninety-four patients with node-positive OCSCC treated with primary surgery and appropriate adjuvant therapy during the year 2011 were evaluated. Surgical histopathology slides of all patients were reviewed, and ENE was graded according to the grading system proposed by Lewis Jr et al. RESULTS: On univariate analysis, lymph node density (LND) greater than or equal to 0.12 (P = 0.013), the presence of ENE in more than two nodes (P = 0.006), and ENE grade 3 through 4 (P = 0.035) were associated with worse (OS). Conventional prognostic factors such as tumor (T) stage, nodal (N) stage, stage grouping, depth of invasion, and pattern of invasion did not have a significant impact on OS. On multivariate analysis, the presence of ENE in more than two nodes (P = 0.018) independently predicted a worse OS. Extranodal extension grade 3 through 4 showed a trend toward significance (P = 0.08). A combination of LND greater than or equal to 0.12, ENE grade 3 through 4, and ENE in more than two lymph nodes conferred the poorest prognosis (3-year OS: 18%; P = 0.000). CONCLUSION: In patients with ENE and advanced nodal disease, T stage, N stage, stage group, depth, and pattern of invasion lose their impact on OS. In patients with ENE, nodal characteristics such as LND, the number of nodes with ENE, and grade of ENE serve as important prognosticators and aid in further risk stratification. LEVEL OF EVIDENCE: 4 Laryngoscope, 129:1130-1136, 2019.

Influence of comorbidity on therapeutic decision making and impact on outcomes in patients with head and neck squamous cell cancers: Results from a prospective cohort study.

BACKGROUND: High prevalence of comorbidity in head and neck squamous cell carcinoma (HNSCC) often lead to suboptimal treatment. The presence study aims to evaluate the presence of comorbidity, its impact on therapeutic decision making, treatment compliance, and overall survival in HNSCC. METHODS: Five hundred eighteen patients with nonmetastatic HNSCC, elder than 18 years of age, without any prior history of cancer or anticancer treatment in the last 5 years were evaluated using Adult Comorbidity Evaluation 27 (ACE 27) index. RESULTS: Two hundred ninety three (56.6%) patients had comorbidity, and 20.6% had deviation from the ideal treatment plan. Higher grade of comorbidity led to less likely completion of guideline-concordant therapy (moderate ACE 27 vs none: odds ratio [OR] 0.46, 95% confidence interval [CI] 0.26-0.82, P < .01*; severe ACE 27 vs none: OR 0.23, 95% CI 0.08-0.57, P < .01*). Patients who completed guideline-concordant treatment had the best outcomes as compared to those who could not (median survival: not reached vs 9.56 months, hazard ratio 3.66, 95% CI: 2.8-4.79; P < .01*). CONCLUSION: Presence of increasing severity of comorbidity in HNSCC influences therapeutic decision making. Survival outcomes are poorer in patients receiving guideline-discordant treatment.