Reduced frequency dosing of osimertinib in EGFR-mutant non-small cell lung carcinoma: real world data.

Introduction: Osimertinib is more efficacious and as safe as first-generation epidermal growth factor receptor (EGFR)-directed tyrosine kinase inhibitors. However, osimertinib is not affordable for most patients in developing nations. Moreover, the minimum biologically effective dose of osimertinib may be less than the approved dose. Materials and methods: This was a retrospective observational multicentric study aimed to describe the efficacy (objective response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS)) and toxicity of osimertinib 80 mg orally administered less frequently than daily (ranging from every other day to once-a-week) in patients with EGFR-mutated non-small cell lung cancer. Results: Between January 2021 and August 2023, we enrolled 22 patients. Six received osimertinib 80 mg once-a-week, nine received 80 mg once-in-3-days and seven received 80 mg on alternate days. Responses included 0 complete responses, 7 (31.8%) partial responses, 9 (40.9%) stable disease and 5 (22.7%) progressive disease. ORR was 31.8%, and DCR was 72.7%. Median PFS was 9.2 months (95% confidence interval (CI) 2.9-15.7), and median OS was 17.8 months (95% CI, 3.2-32.6). In patients who received reduced frequency osimertinib in the second line and beyond, the ORR was 29.4%, DCR was 70.5%, median PFS was 5.9 months (95% CI, 1.1-10.6) and median OS was 17.6 months (95% CI, 2.9-32.2). Grade 3 and higher toxicities were noted in 8 (36.3%) patients. Conclusion: Less frequent dosing of osimertinib may be a valid treatment option, especially in the second line and beyond setting in patients who cannot afford full dose daily osimertinib. This may provide an additional treatment option with a similar toxicity profile as that of standard dose osimertinib.

Myofibrosarcoma of Maxilla - Case Report and Review of Literature.

Myofibrosarcoma is a distinct mesenchymal malignancy which commonly occurs in head and neck region. It has a high tendency for local recurrence and distant metastasis. 39-year-old male presented with epistaxis, nasal obstruction and left sided complete loss of vision. He underwent functional endoscopic sinus surgery and guided biopsy. MRI scan showed a lesion epicentred in the left maxillary sinus, superiorly extending into the orbit. He underwent Class 4b maxillectomy with neck dissection, tracheostomy and free flap reconstruction. Histopathological examination yielded final diagnosis as myofibrosarcoma of maxilla. The patient was planned for adjuvant radiotherapy and has been disease free for 3 years.

Identification of Rare EIF3E::RSPO2 Fusion in Recurrent and Aggressive Urachal Adenocarcinoma.

INTRODUCTION: Urachal cancer (UC) is a rare genitourinary malignancy arising from the urachus, an embryonic remnant of the placental allantois. Its diagnosis remains ambiguous with late-stage cancer detection and represents a highly aggressive disease. Due to its rarity, there is no clear consensus on molecular signatures and appropriate clinical management of UC. CASE REPORT: We report a 45-year-old man with recurrent urachal adenocarcinoma (UA) treated with cystectomies, chemotherapy, and radiotherapy. The patient initially presented with hematuria and abdominal pain. Imaging revealed a nodular mass arising from the superior wall of the urinary bladder and extending to the urachus. Biopsy results suggested moderately differentiated UA with muscle layer involvement. The tumor recurred after 20 months, following which, another partial cystectomy was performed. Repeat progression was noted indicating highly aggressive disease. Targeted next-generation sequencing revealed the presence of EIF3E::RSPO2 fusion, along with BRAF and TP53 mutations, and EGFR gene amplification. This is the first case reporting the presence of this fusion in UA. Palliative medication and radiotherapy were administered to manage the disease. CONCLUSION: Current treatment modality of surgery may be effective in the early stages of recurrent UA; however, a standard chemotherapy and radiotherapy regimen is yet to be determined for advanced stages. The detection of the rare EIF3E::RSPO2 fusion warrants further studies on the significance of this variant as a possible therapeutic target for improved clinical management.

The Impact of Baseline Vitamin D Level in Patients Receiving Gefitinib-Directed Therapy for EGFR-Mutant Non-Small-Cell Lung Cancer.

Background: There is contradicting evidence on vitamin D levels and cancer mortality rates. In this study, we aimed to evaluate the impact of baseline vitamin D level on the outcome in patients with estimated glomerular filtration rate (EGFR)-mutant advanced non-small-cell lung cancer (NSCLC) who received either gefitinib or gefitinib with chemotherapy (pemetrexed and carboplatin) as first-line therapy in a prospective randomized study. Methods: This was a post hoc analysis of a phase III randomized trial comparing gefitinib with gefitinib with carboplatin and pemetrexed in patients with advanced NSCLC with activating EGFR mutations in the first-line setting. As a part of regular practice, baseline vitamin D levels were measured using circulating 25(OH) levels in blood. We included 334 patients who had baseline vitamin D levels in the study and evaluated the effect of the vitamin D level on oncologic outcomes. Results: There were 136 (40.7%) patients with a sufficient (>20 ng/mL) baseline vitamin D level, and 198 (59.3%) patients who were deficient in vitamin D (<20 ng/mL). The median progression-free survival (PFS) in patients with normal vitamin D levels was 17 months, whereas that in patients with deficient vitamin D levels was 15 months, with a hazard ratio of 1.45 (95% confidence interval [CI] = 1.03-2.06). The median overall survival (OS) in patients with normal vitamin D levels was 28.6 months, whereas that in patients with deficient vitamin D levels was 28.5 months, with a hazard ratio of 1.17 (95% CI = 0.81-1.68). On multivariate analysis, only 2 factors impacted the PFS, the baseline vitamin D level, and the treatment regimen; other factors like age, sex, disease stage, and performance status did not. Conclusions: Baseline vitamin D levels have a significant impact on PFS, whereas OS is not affected by the baseline vitamin D levels on patients receiving targeted therapy for EGFR-mutant lung cancer. Trial registration: The trial was prospectively registered with the Clinical Trial Registry of India, registration number CTRI/2016/08/007149. The date of the registration was 5 August 2016.

PRRT with Lu-177 DOTATATE in Treatment-Refractory Progressive Meningioma: Initial Experience from a Tertiary-Care Neuro-Oncology Center.

PURPOSE: Refractory and/or recurrent meningiomas have poor outcomes, and the treatment options are limited. Peptide receptor radionuclide therapy (PRRT) has been used in this setting with promising results. We have documented our experience of using intravenous (IV) and intra-arterial (IA) approaches of Lu-177 DOTATATE PRRT. METHODS: Eight patients with relapsed/refractory high-grade meningioma received PRRT with Lu-177 DOTATATE by IV and an IA route. At least 2 cycles were administered. Time to progression was calculated from the first PRRT session to progression. The response was assessed on MRI using RANO criteria, and visual analysis of uptake was done on Ga-68 DOTANOC PET/CT. Post-therapy dosimetry calculations for estimating the absorbed dose were performed. RESULTS: Median time to progression was 8.9 months. One patient showed disease progression, whereas seven patients showed stable disease at 4 weeks following 2 cycles of PRRT. Dosimetric analysis showed higher dose and retention time by IA approach. No significant peri-procedural or PRRT associated toxicity was seen. CONCLUSION: PRRT is a safe and effective therapeutic option for relapsed/refractory meningioma. The IA approach yields better dose delivery and should be routinely practised.

RET Alterations Differentiate Molecular Profile of Medullary Thyroid Cancer.

PURPOSE: Medullary thyroid cancer (MTC) is a rare cancer originating from parafollicular C cells of the thyroid gland. Therapeutically relevant alterations in MTC are predominantly reported in RET oncogene, and lower-frequency alterations are reported in KRAS and BRAF. Nevertheless, there is an unmet need existing to analyze the MTC in the Indian cohort by using in-depth sequencing techniques that go beyond the identification of known therapeutic biomarkers. MATERIALS AND METHODS: Here, we characterize MTC using integrative whole-exome and whole-transcriptome sequencing of 32 MTC tissue samples. We performed clinically relevant variant analysis, molecular pathway analysis, tumor immune-microenvironment analysis, and structural characterization of RET novel mutation. RESULTS: Mutational landscape analysis shows expected RET mutations in 50% of the cases. Furthermore, we observed mutations in known cancer genes like KRAS, HRAS, SF3B1, and BRAF to be altered only in the RET-negative cohort. Pathway analysis showed differential enrichment of mutations in transcriptional deregulation genes in the RET-negative cohort. Furthermore, we observed novel RET kinase domain mutation Y900S showing affinity to RET inhibitors accessed via molecular docking and molecular dynamics simulation. CONCLUSION: Altogether, this study provides a detailed genomic characterization of patients with MTC of Indian origin, highlighting the possible utility of targeted therapies in this disease.

Gefitinib vs Gefitinib Plus Pemetrexed and Carboplatin Chemotherapy in EGFR-Variant Lung Cancer-Long-Term Results of a Randomized Clinical Trial.

This randomized clinical trial examines whether adding chemotherapy with pemetrexed and carboplatin to gefitinib improves survival among patients with epidermal growth factor receptor (EGFR)­variant non­small cell lung cancer.

Robotic Neck Dissection in Head and Neck Cancer via Modified BABA Technique.

INTRODUCTION: Neck dissection forms an important component in the surgical management of head and neck cancers. By using the conventional techniques of neck dissection, a conspicuous scar is inevitable for the patients. The development of robotic assisted neck dissection provides for a scar-free neck along with good oncological and functional outcomes. METHODS: A prospective observational study was conducted in our institute from 2020 March to 2022 March, where robotic-assisted neck dissections performed via the modified bilateral axillo-breast insufflation technique. RESULTS: Eighty-two patients underwent robotic neck dissections in our institute. Notably, 79 patients were treatment-naïve. The average docking time was 12 min and console time was 160 ± 15 min. The mean lymph node yield was 28.2. The average post-operative stay was 5.6 days. The average follow-up was noted to be 6.4 months. The mean cosmetic satisfaction score in our patients was 4.45. Only one patient presented with nodal recurrence, who was identified as a defaulter for adjuvant treatment. Robotic neck dissection gives similar functional and oncological outcomes as compared with conventional neck dissection. Patients had excellent cosmetic satisfaction following the procedure. The limitations of these techniques include high cost of procedure and longer operating time. This is a level IV evidence study. CONCLUSION: Although good oncological, functional, and cosmetic outcomes have been attained in robotic assisted neck dissection, further randomized controlled studies need to be conducted to justify the added costs, cosmetic advantage, and the time taken. LEVEL OF EVIDENCE: Level IV Laryngoscope, 2024.

Transoral Robotic Surgery for a Rare Case of Venolymphatic Malformation in Parapharyngeal Space.

Venous malformations are low flow endothelial malformations with aberrant and ectatic venous channels. They are defects in vascular growth which causes functional and cosmetic impairment. Gradual growth in size of the lesion occurs due to venous congestion or thrombosis. Venous malformations in parapharyngeal space are a rare entity and are difficult to diagnose. Case Report. 13 year old boy presented with a history of hyposmia and progressive difficulty in breathing for a duration of 2.5 years. MRI face and neck with contrast showed a 4.5 × 4.3x3.6 cm lesion in the left parapharyngeal space. CT angiogram of brain and neck demonstrated a heterogeneously enhancing mass in the left parapharyngeal region. PET scan illustrated an ill-defined mass in the left pre styloid parapharyngeal space. Biopsy from the lesion showed features consistent with venolymphatic malformation. Flexible laryngoscopy showed a bulge over the left soft palate region with narrowing of nasopharyngeal lumen. Patient underwent transoral robotic surgery for complete excision of the mass. Post-operative period was uneventful. He has been on follow up for the past 1 year with no evidence of any residual or recurrent disease. Venolymphatic malformation is a rare lesion in the parapharyngeal space which is difficult to diagnose pre operatively. Surgical excision is the preferred modality of treatment for deep seated lesions in the parapharyngeal space. The advent of transoral robotic surgery have reduced the morbidity and improved clearance for such cases.

Clinical Profile and Outcomes of Carcinoma Penis Patients Receiving Systemic Therapy at an Indian tertiary care Center: A Retrospective Observational Study.

BACKGROUND: Penile cancer is a rare malignancy with scant data on the impact of systemic therapy on outcomes. METHODS: Retrospective observational study of patients with a histological diagnosis of carcinoma penis treated with systemic therapy at the Tata Memorial Centre (Mumbai, India) between August 2010 and February 2018. Primary objective was overall survival (OS); secondary objectives included assessment of clinical characteristics, treatment approaches, and toxicity profiles. RESULTS: We included 91 patients with penile carcinoma who received systemic therapy at our center. Intent of therapy was curative in 71 patients (78%), and palliative in 20 (22%). Median age was 57 years (interquartile range [IQR], 50-65.5) for curatively treated patients and 58.5 years (IQR, 44-65.2) for those with advanced disease. Common presenting symptoms were lumps (70%), and pain (57%). Neoadjuvant chemotherapy (NACT) with paclitaxel + platinum was administered to 19 patients (20.9%), of which 7 (37%) attained complete or partial response. Six patients (31.5%) underwent R0 surgery post-NACT. All 71 patients underwent primary surgery; 47 (66.2%) undergoing partial penectomy. Of the 20 patients treated with palliative first-line chemotherapy, 4(20%) attained a partial response. Median OS of patients treated in curative and palliative settings was 33.8 months (95% CI, 17.2-not recorded) and 11.4 months (95% CI, 9.53-23.3), respectively. CONCLUSIONS: Patients with penile cancer treated with systemic therapy have poor outcomes. Little over a third of the patients respond to neoadjuvant chemotherapy and those with advanced disease have poor survival despite systemic therapy, emphasizing the need for early detection and optimum management of primary and nodal disease.

A Rare Case Report of Osteosarcoma of Maxilla with Double Free-Flap Reconstruction.

Osteosarcomas are rare and highly malignant bone tumours which are composed of malignant mesenchymal cells producing osteoid or immature bone. Maxillary osteosarcomas are rare tumours accounting for less than 1% of head and neck malignancies. Aggressive surgical resection is the main modality of treatment with good reconstruction. Due to the complex anatomy and location of maxilla as well as its proximity to the skull, resection with negative margins is always a challenge and so is the reconstruction so as to reduce the morbidity of the patient and to also give a good functional and cosmetic outcome. Clinical outcomes can be improved with administration of neoadjuvant or adjuvant chemotherapy in selected cases and radiotherapy in case of positive margins. A 41-year-old male patient presented to the outpatient department with complaints of a bulge over the hard palate for the past 1 year. CT scan showed a 6 × 5 × 4 cm osseous expansile lesion arising from the maxillary bone. Biopsy of the tumour showed features of conventional high-grade osteosarcoma. Plate-preserving maxillectomy with tracheostomy was done followed by reconstruction with a double free flap. On post-operative day 1, the flap showed signs of venous congestion and a new free anterolateral thigh flap was done. Patient was discharged on day 7 with a Ryles tube and a tracheostomy tube in situ. Final histopathological examination showed that the tumour was a high-grade chondroblastic osteosarcoma. After regular post-operative visits in the outpatient department and evaluation with flexible laryngoscopy, patient was started on oral feed by day 10 and decannulated by day 15. He has been on regular follow-up for the past 1 year and shows no signs of recurrence or residual disease on clinical examination as well as imaging. Maxillary osteosarcoma is a rare bone tumour which requires accurate imaging and biopsy for accurate surgical planning. The ideal treatment modality is radical resection with negative margins and appropriate reconstruction. With the advent of microvascular surgery, free flaps form the backbone for reconstruction of such large defects.

Deep-Learning-Based Predictive Imaging Biomarker Model for EGFR Mutation Status in Non-Small Cell Lung Cancer from CT Imaging.

PURPOSE: The authors aimed to develop and validate deep-learning-based radiogenomic (DLR) models and radiomic signatures to predict the EGFR mutation in patients with NSCLC, and to assess the semantic and clinical features that can contribute to detecting EGFR mutations. METHODS: Using 990 patients from two NSCLC trials, we employed an end-to-end pipeline analyzing CT images without precise segmentation. Two 3D convolutional neural networks segmented lung masses and nodules. RESULTS: The combined radiomics and DLR model achieved an AUC of 0.88 ± 0.03 in predicting EGFR mutation status, outperforming individual models. Semantic features further improved the model's accuracy, with an AUC of 0.88 ± 0.05. CT semantic features that were found to be significantly associated with EGFR mutations were pure solid tumours with no associated ground glass component (p < 0.03), the absence of peripheral emphysema (p < 0.03), the presence of pleural retraction (p = 0.004), the presence of fissure attachment (p = 0.001), the presence of metastatic nodules in both the tumour-containing lobe (p = 0.001) and the non-tumour-containing lobe (p = 0.001), the presence of ipsilateral pleural effusion (p = 0.04), and average enhancement of the tumour mass above 54 HU (p < 0.001). CONCLUSIONS: This AI-based radiomics and DLR model demonstrated high accuracy in predicting EGFR mutation, serving as a non-invasive and user-friendly imaging biomarker for EGFR mutation status prediction.

Clinical characteristics, outcomes and prognostic factors in KRAS mutant lung cancers: experience from a tertiary care cancer center in India.

Objectives: Kirsten rat sarcoma viral oncogene homologue (KRAS) mutations in lung cancers, long considered untargetable, have had a recent rise in interest due to promising data of agents targeting KRAS p.G12C. As Indian data are scarce, we sought to identify baseline clinical characteristics, prognostic factors and outcomes of lung cancer patients with KRAS mutations at our hospital. Methods: Patients with KRAS mutant lung cancers treated at our institute from 2016 to 2022 were analysed. Results: 133 patients with KRAS mutant lung cancers were identified. Median age was 57 (interquartile range 28-78) years, and 58 (43.6%) were smokers. 17 (12.7%) had brain metastases. The commonest variant was p.G12C, seen in 53 (39.8%) patients. Six (4.5%) had programmed death ligand 1 (PDL-1) expression >50% by Ventana SP263 PDL-1 assay, and 13 (9.7%) had epidermal growth factor mutation. Of 92 patients with available treatment details, the majority received intravenous chemotherapy, nine (9.8%) received tyrosine kinase inhibitors and four (4.4%) received immunotherapy (pembrolizumab). Median progression-free survival (PFS) with first-line therapy was 6 (95% confidence interval (CI) 2.8-9.2) months and median overall survival (OS) was 12 (CI 9.2-14.8) months. The incidence of brain metastases was higher in patients with G12C mutations (p = 0.025). Brain metastases (HR: 3.57, p < 0.001), Eastern Cooperative Oncology Group performance status (PS) ≥ 2 (HR: 2.13, p = 0.002) and G12C mutation (HR: 1.84, p = 0.011) were associated with inferior PFS, while brain metastases (HR: 4.6, p < 0.001), PS ≥ 2 (HR: 2.33, p = 0.001) and G12C mutation (HR: 1.93, p = 0.01) were associated with inferior OS. Conclusion: This is the largest dataset of KRAS mutant lung cancers from India. Brain metastases were higher in patients with G12C mutations and associated with poorer PFS and OS. G12C mutation and PS ≥ 2 were also associated with inferior PFS and OS. Experience with targeted therapy for KRAS mutations remains an area of future exploration due to the unavailability of these agents in India.

Extraskeletal Myxoid Chondrosarcoma of Floor of Mouth-A Rare Case Report and Review of Literature.

Introduction: Chondrosarcomas are rare malignancies of the cartilage and myxoid chondrosarcoma is its variant which commonly occurs in soft tissue of extremities. Extraskeletal chondrosarcoma is a rare malignant neoplasm of bone or soft tissue origin and is characterized by the presence of spindle cells admixed with well differentiated cartilage or chondroid stroma. They are mostly radioresistant tumours and surgical resections with adequate margins is considered as the ideal treatment modality with adjuvant radiotherapy in high grade tumours and add on chemotherapy, in case of presence of poor prognostic factors. Case Report: A 51-year-old diabetic, hypertensive female patient presented to our outpatient department with difficulty in chewing food for a duration of 6 months. On clinical examination, she had an ulceroproliferative growth involving right lower alveolus and floor of mouth. MRI face and neck with contrast showed a 4.1 × 2.9 × 4.5 cm lesion involving right lower alveolus extending to floor of mouth. Biopsy showed features of extraskeletal myxoid chondrosarcoma. She was planned for upfront surgery (Right composite resection with modified radical neck dissection with free fibula flap). Patient was stable post-surgery and was discharged in stable condition. Final histopathology report was high grade myxoid chondrosarcoma. The case was presented in tumour board and the patient was planned for adjuvant radiotherapy. She has been on regular follow up for the past 2 years and shows no signs of recurrence. Conclusion: Extraskeletal myxoid chondrosarcoma of oral cavity is a rare entity and very few cases are reported. It is a malignant neoplasm which is diagnosed with the help of immunohistochemistry. Surgery is the ideal modality of treatment accompanied by adjuvant radiotherapy in cases of high-grade tumours.

Clinical outcomes of ROS1-positive non-small cell lung cancer with limited access to ROS1-tyrosine kinase inhibitors (TKIs): experience from an Indian tertiary referral centre.

Introduction: ROS1 as a driver mutation is observed in approximately 1%-2% of all non-small cell lung cancer (NSCLC). Given its rarity, we share our experience regarding ROS1-positive NSCLC including the access to ROS1 tyrosine kinase inhibitors (TKIs) in a low-middle income country like India. Methods: It is a retrospective analysis of ROS1-positive NSCLC patients registered between January 2015 to December 2021 for demographics, treatment patterns and outcomes i.e., overall survival (OS) and progression free survival (PFS). Results: Baseline characteristics were available for 70 patients of 78 patients positive for ROS1 by fluorescent in situ hybridisation. Median age at presentation was 52 years, 39 (55.7%) were males, most (51, 72.86%) were non-smokers and ten patients (14.3%) had poor Eastern Cooperative Oncology Group (ECOG) performance status (PS) i.e., PS >2 at presentation. A total of 67 patients receiving cancer directed therapy were analysed for survival. The first line (1L) therapies included - ROS1 TKIs in 38, chemotherapy in 20, epidermal growth factor receptor TKI in eight and chemotherapy-bevacizumab in one only. ROS1 TKI was provided to 20 patients as part of an assistance programme. The median OS for patients who received ROS1 TKI was not attained (95% CI 37.85-NA), while it was 8.11 (95% CI 6.31-NA) months for those who did not (HR-0.1673). The median PFS for the 1L ROS1 TKI compared to the no-TKI group was 27.07 (95% CI 24.28-NA) months versus 5.78 (95% CI 3.42-12) months (HR: 0.2047). Poor ECOG PS at presentation was the only independent prognosticator for survival. Conclusion: Using ROS1 TKI improves clinical outcomes in all-comers though statistically not significant. To further improve outcomes, future trials should pay special attention to patients with poor PS and find a way to increase the current limited access to TKI.

Assessment of quality of life in thyroid cancer patients using the EORTC thyroid-specific questionnaire: a prospective cross-sectional study.

BACKGROUND: Many studies on the quality of life (QoL) among the thyroid cancer survivors have shown conflicting results. This may be since many of these studies have not used thyroid cancer-specific questionnaires. PATIENTS AND METHODS: In our study we have translated the EORTC THY-34, validated and served it in a cross-sectional study to the assess the QoL among thyroid cancer patients free of disease during their routine follow-up. Patients were categorized based on the duration from treatment completion, ATA risk stratification, treatment received, number of RAI sessions and thyroid function status during analysis. RESULTS: Overall, 220 thyroid cancer survivors were included in this study. In general, in the EORTC QLQ-C30, the global QoL of thyroid cancer patients were good with a mean score of 72.99. The highest score was that for social functioning (89.55). In the EORTC-THY34 all the patients in the cohort had relatively lower scores (on symptom scales). Overall, there was no difference in the QLQ-C30 and THY-34 QoL with respect to any of the categorization mentioned above. However, our thyroid cancer patients QoL scores were better and/or comparable to those in published literature and they were also better or comparable to the QoL of the general population those were available in literature. CONCLUSIONS: There was no difference in the QoL scores based on various categories. To better understand the quality of life of these patients a prospective longitudinal study with baseline values and values at regular intervals might give us a better insight.

Phase 3 RCT comparing docetaxel-platinum with docetaxel-platinum-5FU as neoadjuvant chemotherapy in borderline resectable oral cancer.

BACKGROUND: Neoadjuvant chemotherapy (NACT) with TPF (docetaxel, cisplatin, and 5FU) is one of the treatment options in very locally advanced oral cancer with a survival advantage over PF (cisplatin and 5FU). TP (docetaxel and cisplatin) has shown promising results with a lower rate of adverse events but has never been compared to TPF. METHODS: In this phase 3 randomized superiority study, adult patients with borderline resectable locally advanced oral cancers were randomized in a 1:1 fashion to either TP or TPF. After the administration of 2 cycles, patients were evaluated in a multidisciplinary clinic and further treatment was planned. The primary endpoint was overall survival (OS) and secondary endpoints were progression-free survival (PFS) and adverse events. RESULTS: 495 patients were randomized in this study, 248 patients in TP arm and 247 in TPF arm. The 5-year OS was 18.5% (95% CI 13.8-23.7) and 23.9% (95% CI 18.1-30.1) in TP and TPF arms, respectively (Hazard ratio 0.778; 95% CI 0.637-0.952; P = 0.015). Following NACT, 43.8% were deemed resectable, but 34.5% underwent surgery. The 5-year OS was 50.7% (95% CI 41.5-59.1) and 5% (95%CI 2.9-8.1), respectively, in the surgically resected versus unresected cohort post NACT (P < 0.0001). Grade 3 or above adverse events were seen in 97 (39.1%) and 179 (72.5%) patients in the TP and TPF arms, respectively (P < 0.0001). CONCLUSION: NACT with TPF has a survival benefit over TP in borderline resectable oral cancers, with an increase in toxicity which is manageable. Patients who undergo surgery achieve a relatively good, sustained survival.

A Comparative Study Evaluating the Quality of Life and Survival Outcomes in Patients Receiving Chemotherapy Versus Oral Tyrosine Kinase Inhibitor in the Third Line and Beyond Setting for Advanced NSCLC.

Introduction: The outcomes in advanced NSCLC have improved owing to the availability of more effective systemic and improved supportive care. This has increased the number of patients who seek treatment in the third line and beyond setting. We conducted this study to compare the quality of life (QoL), toxicity, and outcomes in patients receiving chemotherapy and EGFR tyrosine kinase inhibitors (TKIs) in this setting. Methods: In this phase 3, randomized, open-label study, patients with stage III or IV NSCLC with disease progression on at least two prior lines of chemotherapy, with a life expectancy of at least 3 months, without prior EGFR TKI exposure, and stable brain metastases (if any) were included. Patients were randomized to receive chemotherapy (gemcitabine or docetaxel or paclitaxel or vinorelbine) or an EGFR TKI (erlotinib or gefitinib). The primary end point was the change in QoL at 8 to 10 weeks; the secondary outcomes were safety and overall survival (OS). Patients underwent clinical evaluation at every visit, and toxicity was assessed as per Common Terminology Criteria for Adverse Events version 4.03. A radiological tumor response assessment was done every 8 to 12 weeks from the start of therapy. The QoL was assessed using the EORTC QLQ C30 and LC13 questionnaires. The change in QoL scores was calculated as the difference between scores at baseline and scores at 8 to 10 weeks (Δ) for each QoL domain. The Mann-Whitney U test was used to compare the mean difference (Δ) for each domain. OS and progression-free survival (PFS) were determined using the Kaplan-Meier method and Cox proportional regression analysis. Results: A total of 246 patients were enrolled in the study, with 123 in each arm. There was a male predominance with 69.1% male patients in the chemotherapy arm and 70.7% in the EGFR TKI arm. The median age of patients in the chemotherapy arm was 54 years and 55 years in the chemotherapy and EGFR TKI arms, respectively. There was no significant difference in the change in QoL at baseline and the second visit (Δ) in both arms in all domains of EORTC QLQ C30 except cognitive function (p = 0.0045) and LC13 except alopecia (0.01249). The mean Δ Global Health Status was -28 in the chemotherapy arm and -26.8 in the EGFR TKI arm; this was not statistically significant (p = 0.973). The median follow-up was 88.1 months (95% confidence interval [CI]: 39.04-137.15). On the intention-to-treat analysis, the median PFS was 3.13 months (95% CI: 2.15-4.11) in the chemotherapy arm and 2.26 months (95% CI: 2.1-2.43) in the EGFR TKI arm, with hazard ratio at 1.074 (95% CI: 0.83-1.38) (p = 0.58). There were 120 deaths in each arm. The median OS was 7.63 months (95% CI: 5.96-9.30) in the chemotherapy arm and 7.5 months in the EGFR TKI arm (95% CI: 5.85-9.14); hazard ratio at 1.033 (95% CI: 0.80-1.33) (p = 0.805). The toxicity profile was similar in both arms except for a significantly higher incidence of fatigue (p = 0.043), peripheral neuropathy (0.000), alopecia, hypokalemia (0.037), and pedal edema (0.007) in the chemotherapy arm and dry skin (p = 0.000) and skin rash (p = 0.019) in the EGFR TKI arm. Conclusions: There was no significant difference in most QoL scales (except cognitive function and alopecia), OS, and PFS of patients with advanced NSCLC receiving an EGFR TKI as compared with chemotherapy TKI in the third-line setting. The toxicity profile is consistent with the known toxicities of the agents.

Long-term outcomes of neo-adjuvant chemotherapy on borderline resectable oral cavity cancers: Real-world data of 3266 patients and implications for clinical practice.

BACKGROUND: Neo-adjuvant chemotherapy (NACT) followed by response assessment is the standard treatment algorithm for locally advanced oral cavity squamous cell carcinomas (OCSCC) in the Indian subcontinent. The 3-drug NACT regimen (Docetaxel-Cisplatin-5-FU) has shown improvement in overall survival over 2-drug regimen (Docetaxel-Cisplatin) in a phase-3 randomised study. We have analysed the 10-year outcomes with this treatment algorithm. METHODS: This was an institutional review board approved retrospective analysis of a prospectively collected dataset of borderline resectable OCSCC patients who underwent NACT. Patients who became resectable after NACT underwent surgery followed by appropriate adjuvant therapy. Patients who were unresectable received definitive chemoradiation (CTRT), palliative chemotherapy, radiotherapy or best supportive care based on general condition. RESULTS: A total of 3266 patients were included. The most common subsite was buccal mucosa and the most frequent indication was peri-tumoral edema upto zygoma. More than 2-drugs NACT was offered to 32.9% patients. Overall, 32.5% patients had a response to NACT. A total of 1358 patients were offered curative treatment, of which 929 (32%) underwent surgery and the rest underwent definitive chemo-radiation (14.8%). Patients who received more than 2-drugs NACT versus those who received 2-drugs had a 10-years OS of 21% vs 5.1% (p < 0.001). Patients who underwent surgery versus those who did not had a 10-year OS of 21.8% vs 4.1% (p < 0.001). Patients who achieved pCR had a 5-year OS of 45.3% vs 13.3% for those who did not (p < 0.001). CONCLUSION: NACT leads to long term survival benefit in patients of borderline resectable oral cavity cancer.