Evaluation of quantitative imaging parameters in head and neck squamous cell carcinoma.

BACKGROUND: Functional imaging such as 18F-fluoro-deoxy-glucose positron emission tomography/computed tomography (FDG-PET/CT), 18F-fluoro-misonidazole (F-MISO)-PET/CT, and diffusion-weighted magnetic resonance imaging (DW-MRI) can assess complex biological phenomena in tumors reflecting underlying disease biology. The aim of this prospective observational study was to correlate quantitative imaging parameters derived from pretreatment biological imaging such as FDG-PET/CT, F-MISO-PET/CT, and DW-MRI with each other and with clinical outcomes in patients with head and neck squamous cell carcinoma (HNSCC) treated with definitive radio(chemo)therapy. METHODS: Twenty patients with pharyngo-laryngeal cancers underwent pretreatment biological imaging. Gross tumor volume (GTV) was delineated on axial planning CT (GTVCT). Quantitative FDG-PET/CT parameters included maximum, mean, minimum standardized uptake values (SUVmax-FDG, SUVmean-FDG, SUVmin-FDG); metabolic tumor volume (MTV); and total lesion glycolysis (TLG). F-MISO-PET/CT parameters included hypoxic tumor volume (HTV); maximum, mean, minimum SUV; and fractional hypoxic volume (FHV). Mean apparent diffusion coefficient (ADCmean) was derived from DW-MRI. RESULTS: There was moderately strong positive correlation (r=0.616, P=0.005) between GTVCT and MTV. HTV derived from F-MISO-PET/CT at 3-hours (HTV3hrs-F-MISO) showed strong positive correlation with GTVCT (r=0.753, P<0.0001) and MTV (r=0.796, P<0.0001) respectively. ADCmean showed strong positive correlations with SUVmean-5hrs-F-MISO (r=0.713, P=0.021) and SUVmin-5hrs-F-MISO (r=0.731, P=0.016) respectively. A moderate negative correlation (r=-0.500, P=0.049) was observed between ADCmean and MTV. At a median follow up of 44 months, the 5-year Kaplan-Meier estimates of loco-regional control, disease-free survival, and overall survival were 53%, 43%, and 40% respectively. Larger volume of primary tumor (GTVCT>22cc and MTV>7.9cc) and increasing hypoxia (HTV3hr-F-MSO>4.9cc) were associated with worse outcomes. CONCLUSIONS: Functional imaging represents an attractive and non-invasive modality to assess complex biological phenomena in solid tumors. Larger tumor volume and increasing hypoxia emerged as putative prognostic imaging biomarkers in HNSCC.

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.

A randomized phase 3 trial comparing nimotuzumab plus cisplatin chemoradiotherapy versus cisplatin chemoradiotherapy alone in locally advanced head and neck cancer.

BACKGROUND: Because the addition of nimotuzumab to chemoradiation in patients with locally advanced head and neck cancer improved outcomes in a phase 2 study, the authors conducted a phase 3 study to confirm these findings. METHODS: This open-label, investigator-initiated, phase 3, randomized trial was conducted from 2012 to 2018. Adult patients with locally advanced head and neck cancer who were fit for radical chemoradiation were randomized 1:1 to receive either radical radiotherapy (66-70 grays) with concurrent weekly cisplatin (30 mg/m2 ) (CRT) or the same schedule of CRT with weekly nimotuzumab (200 mg) (NCRT).The primary endpoint was progression-free survival (PFS); key secondary endpoints were disease-free survival (DFS), duration of locoregional control (LRC), and overall survival (OS). An intent-to-treat analysis also was performed. RESULTS: In total, 536 patients were allocated equally to both treatment arms. The median follow-up was 39.13 months. The addition of nimotuzumab improved PFS (hazard ratio [HR], 0.69; 95% CI, 0.53-0.89; P = .004), LRC (HR, 0.67; 95% CI, 0.50-0.89; P = .006), and DFS (HR, 0.71; 95% CI, 0.55-0.92; P = .008) and had a trend toward improved OS (HR, 0.84; 95% CI, 0.65-1.08; P = .163). Grade 3 through 5 adverse events were similar between the 2 arms, except for a higher incidence of mucositis in the NCRT arm (66.7% vs 55.8%; P = .01). CONCLUSIONS: The addition of nimotuzumab to concurrent weekly CRT improves PFS, LRC, and DFS. This combination provides a novel alternative therapeutic option to a 3-weekly schedule of 100 mg/m2 cisplatin in patients with locally advanced head and neck cancer who are treated with radical-intent CRT.

Locoregional treatment versus no treatment of the primary tumour in metastatic breast cancer: an open-label randomised controlled trial.

BACKGROUND: The role of locoregional treatment in women with metastatic breast cancer at first presentation is unclear. Preclinical evidence suggests that such treatment might help the growth of metastatic disease, whereas many retrospective analyses in clinical cohorts have suggested a favourable effect of locoregional treatment in these patients. We aimed to compare the effect of locoregional treatment with no treatment on outcome in women with metastatic breast cancer at initial presentation. METHODS: In this open-label, randomised controlled trial, we recruited previously untreated patients (≤65 years of age with an estimated remaining life expectancy of at least 1 year) presenting with de-novo metastatic breast cancer from Tata Memorial Centre, Mumbai, India. Patients were randomly assigned (1:1) to receive locoregional treatment directed at their primary breast tumour and axillary lymph nodes, or no locoregional treatment, by a computer-generated block randomisation sequence (block size of four). Randomisation was stratified by site of distant metastases, number of metastatic lesions, and hormone receptor status. Patients with resectable primary tumour in the breast that could be treated with endocrine therapy were randomly assigned upfront, whereas those with an unresectable primary tumour were planned for chemotherapy before randomisation. Of the patients who had chemotherapy before randomisation, we randomly assigned patients who had an objective tumour response after six to eight cycles of chemotherapy. The primary endpoint was overall survival analysed by intention to treat. This study is registered with ClinicalTrials.gov, NCT00193778. FINDINGS: Between Feb 7, 2005, and Jan 18, 2013, of the 716 women presenting with de-novo metastatic breast cancer, we randomly assigned 350 patients: 173 to locoregional treatment and 177 to no locoregional treatment. At data cut-off of Nov 1, 2013, median follow-up was 23 months (IQR 12·2-38·7) with 235 deaths (locoregional treatment n=118, no locoregional treatment n=117). Median overall survival was 19·2 months (95% CI 15·98-22·46) in the locoregional treatment group and 20·5 months (16·96-23·98) in the no-locoregional treatment group (HR 1·04, 95% CI 0·81-1·34; p=0·79), and the corresponding 2-year overall survival was 41·9% (95% CI 33·9-49·7) in the locoregional treatment group and 43·0% (35·2-50·8) in the no locoregional treatment group. The only adverse event noted was wound infection related to surgery in one patient in the locoregional treatment group. INTERPRETATION: There is no evidence to suggest that locoregional treatment of the primary tumour affects overall survival in patients with metastatic breast cancer at initial presentation who have responded to front-line chemotherapy, and this procedure should not be part of routine practice.

Volumetric and geometric changes in the parotid glands and target volume during image-guided radiotherapy for locally advanced oropharyngeal cancers.

PURPOSE: This study aimed to evaluate the volumetric and geometric changes in the parotid glands and target volume during image-guided radiotherapy (IGRT) for locally advanced oropharyngeal cancers. MATERIALS AND METHODS: Twenty patients receiving radiotherapy using IGRT at a dose of 70 Gy/35 fractions/7 weeks for locally advanced oropharyngeal cancers were accrued. Radiotherapy planning computed tomography (CT) scans were performed at pre-radiotherapy (RT), 20, 40, and 60 Gy for each patient. Volume changes in target and parotids along with shifts of parotids were assessed with respect to pre-RT scan after co-registration. In study scans, GTVp and GTVn were recontoured as per particular CT. CTV and PTV were copied from planning CT to study CT. CTV was edited from anatomical barriers, and PTV was edited only from the skin in the study CT. The parotids were recontoured on each study scan. The center of mass (COM) of C2 vertebral body was considered as the reference to evaluate its shifts. RESULTS: There was a statistically significant percentage regression of ipsilateral and contralateral parotid mean volumes at the rate of 0.85%/0.207 cc and 0.98%/0.26 cc per day, respectively. We observed the mean medial shift of center of mass of ipsilateral parotid of 2.23 mm (p = 0.011) and contralateral parotid of 2.67 mm (p = 0.069) at the end of 60 Gy. GTVp (mean) reduced from 41.87 cc at 0 Gy to 31.13 cc (25.65%) at 60 Gy (p = 0.003), while GTVn (mean) reduced from 19.98 cc at 0 Gy to 10.79 cc (45.99%) at 60 Gy (p = 0.003). There was a statistically significant reduction in CTV and PTV volumes at 60 Gy. CONCLUSION: Statistically significant volumetric and geometric changes occurred during intensity-modulated radiation (IMRT), which were most prominent after 40 Gy and were maximum at 60 Gy. There was a medial shift of parotid glands toward the high-dose region. This study can be useful to devise an adaptive radiotherapy strategy.

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.

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.

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.

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.

Brachytherapy training in India: Results from the GEC-ESTRO-India survey.

INTRODUCTION: Brachytherapy (BT) is integral in treatment of gynecological malignancies and is also an option for many other cancers. Data on training and proficiency levels of early career oncologists is limited. Like other continents a survey was conducted for early career oncologists in India. METHODS AND MATERIALS: An online survey was conducted from November 2019 to February 2020, through Association of Radiation Oncologists of India (AROI) for early career radiation oncologists expected to be within 6 years of training. The survey used a 22 item questionnaire that was also used for European survey. Responses to individual statements were recorded on a 1-5 Likert-type scale. Descriptive statistics were used to describe proportions. RESULTS: One-hundred twenty-four (17%) of 700 recipients responded to the survey. Majority of the respondents (88%) stated that being able to perform BT at the end of their training was important. Two-thirds of the respondents (81/124) had performed >10 intracavitary procedure and 22.5% had performed >10 intracavitary-interstitial implants. Many respondents had not performed nongynecological procedure- breast (64%), prostate(82%), gastro-intestinal (47%). Respondents predicted that in next 10 years, the role of BT is likely to increase. Lack of dedicated curriculum and training was perceived as the greatest barriers to achieving independence in BT (58%). Respondents suggested that BT training should be prioritized during conferences (73%) and online teaching modules (56%), along with development of BT skills labs (65%). CONCLUSION: This survey identified a lack of proficiency in gynecological intracavitary-interstitial brachytherapy and non-gynecological brachytherapy, despite BT training being regarded as highly important. Dedicated programs, including standardized curriculum and assessment need to be developed for training early- career radiation oncologists in BT.

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.

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.

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].

H&N and Skin (HNS) GEC-ESTRO Working Group critical review of recommendations regarding prescription depth, bolus thickness and maximum dose in skin superficial brachytherapy with flaps and customized moulds.

The aim of this publication is the assessment of the existing guidelines for non-melanoma skin cancer (NMSC) superficial brachytherapy (BT) and make a critical review based on the existing literature about the maximum dose prescription depth, bolus thickness and maximum skin surface dose (Dmax) of the published clinical practice. A systematic review of NMSC superficial BT published articles was carried out by the GEC-ESTRO Head & Neck and Skin (HNS) Working Group (WG). 10 members and 2 external reviewers compared the published clinical procedures with the recommendations in the current guidelines and examined the grade of evidence. Our review verified that there is a large variation among centres with regards to clinical practice in superficial BT and identified studies where published parameters such as maximum dose prescription depth, bolus thickness and Dmax exceed the constraints recommended in the guidelines, while showing excellent results in terms of local control, toxicity and cosmesis. This review confirmed that current recommendations on skin superficial BT do not include published experience on tumours treated with superficial BT that require dose prescription depth beyond the recommended 5 mm under the skin surface and that the existing literature does not provide sufficient evidence to relate dosimetry of superficial BT to patient reported outcome measures. The GEC-ESTRO HNS WG considers acceptable to prescribe superficial BT dose at a depth above 5 mm beyond the skin surface, and modify the bolus thickness to optimize the treatment plan and adjust the acceptable maximum dose on the skin surface, all pending clinical situation.

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.

Clinical Profile and Outcome of Patients With Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer With Brain Metastases: Real-World Experience.

PURPOSE: There are sparse data in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer with brain metastases from real-world settings, especially where access to newer targeted therapies is limited. METHODS: This was a single institution, retrospective cohort study of patients with HER2-positive breast cancer diagnosed between January 2013 and December 2017 to have brain metastases and treated with any HER2-targeted therapy. The main objectives were to estimate progression-free survival (PFS) and overall survival (OS) from the time of brain metastases. RESULTS: A total of 102 patients with a median age of 52 (interquartile range, 45-57) years were included, of whom 63 (61.8%) had received one line and 14 (13.7%) had received two lines of HER2-targeted therapies before brain metastasis, 98 (96.1%) were symptomatic at presentation, 22 (25.3%) had solitary brain lesion, 22 (25.3%) had 2-5 lesions, and 43 (49.4%) had ≥ 5 lesions. Local treatment included surgical resection in nine (8.9%) and radiotherapy in all (100%) patients. The first HER2-targeted therapy after brain metastasis was lapatinib in 71 (68.6%), trastuzumab in 19 (18.6%), lapatinib and trastuzumab in three (2.9%), trastuzumab emtansine in four (3.9%), and intrathecal trastuzumab in five (4.9%) patients. At a median follow-up of 13.9 months, the median PFS and OS were 8 (95% CI, 6.2 to 9.8) months and 14 (95% CI, 10.8 to 17.2) months, respectively, with a 2-year OS of 25% (95% CI, 16.7 to 34.4). The median PFS in patients who received lapatinib-capecitabine regimen (n = 62) was 9.0 (95% CI, 7.3 to 10.7) months. CONCLUSION: There was a substantial clinical benefit of local and systemic therapy in patients with brain metastases and HER2-positive disease in a real-world setting with limited access to newer HER2-targeted drugs.

Survival outcomes with 12 weeks of adjuvant or neoadjuvant trastuzumab in breast cancer.

Background: There is limited access to 1 year of adjuvant trastuzumab in resource-constrained settings. Most randomized studies have failed to prove non-inferiority of shorter durations of adjuvant trastuzumab compared to 1 year However, shorter durations are often used when 1 year is not financially viable. We report the outcomes with 12 weeks of trastuzumab administered as part of curative-intent treatment. Methods: This is a retrospective analysis of patients treated at Tata Memorial Centre, Mumbai, a tertiary care cancer center in India. Patients with human epidermal growth factor receptor (HER2)-positive early or locally advanced breast cancer who received 12 weeks of adjuvant or neoadjuvant trastuzumab with paclitaxel and four cycles of an anthracycline-based regimen in either sequence, through a patient assistance program between January 2011 and December 2012, were analyzed for disease-free survival (DFS), overall survival (OS), and toxicity. Results: A total of 102 patients were analyzed with a data cutoff in September 2019. The median follow-up was 72 months (range 6-90 months), the median age was 46 (24-65) years, 51 (50%) were postmenopausal, 37 (36%) were hormone receptor-positive, and 61 (60%) had stage-III disease. There were 37 DFS events and 26 had OS events. The 5-year DFS was 66% (95% Confidence Interval [CI] 56-75%) and the OS was 76% (95% CI 67-85%), respectively. Cardiac dysfunction developed in 11 (10.7%) patients. Conclusion: The use of neoadjuvant or adjuvant 12-week trastuzumab-paclitaxel in sequence with four anthracycline-based regimens resulted in acceptable long-term outcomes in a group of patients, most of whom had advanced-stage nonmetastatic breast cancer.

The MUSES∗: a prognostic study on 1360 patients with sinonasal cancer undergoing endoscopic surgery-based treatment: ∗MUlti-institutional collaborative Study on Endoscopically treated Sinonasal cancers.

BACKGROUND: Over the last 2 decades, transnasal endoscopic surgery (TES) has become the most frequently employed surgical technique to treat sinonasal malignancies. The rarity and heterogeneity of sinonasal cancers have hampered large non-population-based analyses. METHODOLOGY: All patients receiving TES-including treatment between 1995 and 2021 in 5 referral hospitals were included. A prognostic study was performed, and multivariable models were transformed into nomograms. Training and validation sets were based on results from 3 European and 2 non-European centres, respectively. RESULTS: The training and validation set included 940 and 420 patients, respectively. The mean age at surgery, primary-versus-recurrent presentation, histology distribution, type of surgery, T category and type of adjuvant treatment were differently distributed in the training and validation set. In the training set, 5-year overall survival and recurrence-free survival with a 95%-confidence interval were 72.7% (69.5-76.0%) and 66.4% (63.1-69.8%), respectively, significantly varying with histology. At multivariable analyses, age, gender, previous treatment, the extent of resection on the cranial, lateral and posterolateral axes, grade/subtype, T category, nodal status, margin status and adjuvant treatment were all associated with different prognostic outcomes, displaying a heterogeneous significance and effect size according to histology. The internal and external validation of nomograms was satisfactory (optimism-corrected C-index >0.7 and cumulative area under curve >0.7) for all histologies but mucosal melanoma. CONCLUSIONS: Outcomes of TES-based treatment of sinonasal cancers vary substantially with histology. This large, non-population-based study provides benchmark data on the prognosis of sinonasal cancers that are deemed suitable for treatment including TES.

Diagnostic performance of post-treatment FDG PET or FDG PET/CT imaging in head and neck cancer: a systematic review and meta-analysis.

PURPOSE: Our objective was to conduct a systematic review and meta-analysis of studies assessing the diagnostic performance of (18)F-fluorodeoxyglucose positron emission tomography (FDG PET) with or without computed tomography (CT) in post-treatment response assessment and/or surveillance imaging of head and neck squamous cell carcinoma (HNSCC). METHODS: A systematic search of the indexed medical literature was done using appropriate keywords to identify relevant studies. Metrics of diagnostic test accuracy, viz. sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were extracted from individual studies and combined using a random effects model to yield weighted mean pooled estimates with 95% confidence intervals (95% CI). The impact of timing of post-treatment scan, study quality and advancements in PET technology was explored through meta-regression. RESULTS: A total of 51 studies involving 2,335 patients were included in the meta-analysis. The weighted mean (95% CI) pooled sensitivity, specificity, PPV and NPV of post-treatment FDG PET(CT) for the primary site was 79.9% (73.7-85.2%), 87.5% (85.2-89.5%), 58.6% (52.6-64.5%) and 95.1% (93.5-96.5%), respectively. Similar estimates for the neck were 72.7% (66.6-78.2%), 87.6% (85.7-89.3%), 52.1% (46.6-57.6%) and 94.5% (93.1-95.7%), respectively. Scans done ≥ 12 weeks after completion of definitive therapy had moderately higher diagnostic accuracy on meta-regression analysis using time as a covariate. CONCLUSION: The overall diagnostic performance of post-treatment FDG PET(CT) for response assessment and surveillance imaging of HNSCC is good, but its PPV is somewhat suboptimal. Its NPV remains exceptionally high and a negative post-treatment scan is highly suggestive of absence of viable disease that can guide therapeutic decision-making. Timing of post-treatment imaging has a significant, though moderate impact on diagnostic accuracy.

Objective assessment of swallowing function after definitive concurrent (chemo)radiotherapy in patients with head and neck cancer.

The aim of this study was to objectively assess swallowing function and factors impacting it after curative intent definitive (chemo)radiotherapy (CRT) for head and neck squamous cell carcinoma (HNSCC). Swallowing function was studied in a cohort of 47 patients with locoregionally advanced (T1-4, N0-3) HNSCC treated with definitive CRT. Objective assessment of swallowing function was done using modified barium swallow (MBS) at baseline (pre-CRT) and subsequent follow-ups. Scoring of MBS was done using penetration-aspiration scale (PAS). Abnormal swallowing was defined in terms of incidence and severity of penetration-aspiration, pharyngeal residue, postural change, and regurgitation. Aspiration, residual, postural change, and regurgitation were present on baseline pre-CRT assessment in 9 (19%), 11 (23%), 10 (21%), and 5 (10%) patients that increased to 11 (29%), 11 (29%), 12 (32%), and 10 (26%) patients, respectively, at 6-month post-CRT evaluation. The proportion of patients with high PAS scores (3-7) increased from 27% at baseline to 37% at 6-month post-CRT evaluation. Among patients (n = 34) with low PAS scores (≤2) at baseline, additional impairment of swallowing function was seen in 53 and 46% at 2- and 6-month assessment, respectively. Residue (44%) and aspiration (18%) domains were impaired in a higher proportion of patients after CRT. Thin and thick barium had higher aspiration and residue function impairment, respectively. Patients with pre-CRT poor subjective swallowing function (P = 0.004), hypopharyngeal primary (P = 0.05), and large tumor volume (P = 0.05) had significantly worse objective swallowing function at baseline as demonstrated by pretreatment PAS scores. This study provides useful information regarding patterns of objective swallowing dysfunction in patients treated with definitive (chemo)radiotherapy. There is significant impairment of objective swallowing function in all domains following CRT, with residue and aspiration domains being affected most significantly.