A total of 50 patients with advanced pancreatic cancer were enrolled in a phase II study of bevacizumab 15 mg kg À1 , capecitabine 1300 mg m À2 daily for 2 weeks and gemcitabine 1000 mg m À2 weekly 2 times; cycles were repeated every 21 days. Radiological response rate was 22%; progression-free survival and over survival were 5.8 and 9.8 months respectively. Grade 3 or 4 toxicities included neutropaenia (22%), thrombocytopaenia (14%), thromboembolic events (12%), hypertension (8%) and haemorrhage (6%).

Esophageal adenocarcinoma (EAC) is one of the fastest growing malignancies in the US. The long-term survival of patients with this cancer remains poor; only 25% of patients undergoing surgical excision are alive after 5 years. Multimodal programs that incorporate radiotherapy, chemotherapy and surgery for localized tumors may result in a modest survival advantage. However, significant strides in this disease can result from the inclusion of targeted therapies. The epidermal growth factor receptor (EGFR) family represents one such target and is receiving increasing attention due to the advent of specific inhibitors. Studies conducted by us and others have shown that the overexpression of EGFR family signaling intermediates is common in Barrett’s esophagus and EAC. In the latter case, EGFR expression may have prognostic significance. EGFR inhibitors, including oral tyrosine kinase inhibitors and monoclonal antibodies, result in a synergistic antitumor effect with chemotherapeutic agents or with radiotherapy. Therefore, several ongoing studies include EGFR-directed therapy either alone or in combination with chemoradiotherapy for this disease. Our study of gefitinib, oxaliplatin and radiotherapy suggested that gefitinib can be safely incorporated into an oxaliplatin-based chemoradiation program for esophageal cancer, although the clinical activity of this combination is modest. Herein, we review the current literature on this subject.

Background: There has been an increase an alarming rise in invasive mycoses during COVID-19 pandemic, especially during the second wave. Aims: Compare the incidence of invasive mycoses in the last three years and study the risk factors, manifestations and outcomes of mycoses in the COVID era. Methodology: Multicentric study was conducted across 21 centres in a state of western India over 12-months. The clinico-radiological, laboratory and microbiological features, treatment and outcomes of patients were studied. We also analysed yearly incidence of rhino-orbito-cerebral mycosis. Results: There was more than five-times rise in the incidence of invasive mycoses compared to previous two-years. Of the 122 patients analysed, mucor, aspergillus and dual infection were seen in 86.9%, 4.1%, and 7.4% respectively. Fifty-nine percent had simultaneous mycosis and COVID-19 while rest had sequential infection. Common presenting features were headache (91%), facial pain (78.7%), diplopia (66.4%) and vison loss (56.6%). Rhino-orbito-sinusitis was present in 96.7%, meningitis in 6.6%, intracranial mass lesions in 15.6% and strokes in 14.8%. A total of 91.8% patients were diabetic, while 90.2% were treated with steroids during COVID-19 treatment. Mortality was 34.4%. Conclusion: Invasive fungal infections having high mortality and morbidity have increased burden on already overburdened healthcare system. Past illnesses, COVID-19 itself and its treatment and environmental factors seem responsible for the rise of fungal infection. Awareness and preventive strategies are the need of hours and larger studies are needed for better understanding of this deadly disease.

Background: Guillian--Barre' Syndrome (GBS) has been shown to be associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. The aim of our study was to study the clinical profile and outcomes of GBS in COVID-19 from the Western region of India, the State of Maharashtra. Methods: This was a retrospective, multicenter observation study from different hospitals in Maharashtra beginning from March 2020 until November 2020. Results: We report 42 patients with COVID-19 GBS. Mean age was 59 years (range, 24--85 years). 31/42 (73.8%) were men. GBS was the presenting symptom in 14/42 (33%), while six of them remained asymptomatic for COVID-19 despite positive SARS-CoV-2 on nasopharyngeal swab reverse transcriptase polymerase chain reaction. The median interval between COVID-19 and GBS was 14 days (SD + 11), with minimum of 1 and maximum 40 days. Clinical presentation was like that of typical GBS. Electrophysiological studies showed a predominant demyelinating pattern in 25/42 (59.5%). Inflammatory markers were elevated in 35/42 (83.3%) and 38/42 (90.5%) had an Abnormal high-resolution CT (HRCT) chest. 14/42 (33.3%) patients required a ventilator, with nine deaths. Intravenous immunoglobulin was the mainstay of treatment for GBS. Majority had a good outcome and were walking independently or with minimal support at discharge. In subgroup analysis, the postinfectious group had a better outcome than the parainfectious group. Conclusion: GBS in COVID-19 occurs as both parainfectious and postinfectious GBS. Parainfectious GBS needs more rigorous monitoring and may benefit from COVID-19 specific treatment. Routine screening for SARS-CoV-2 should be implemented in patients with GBS in view of the ongoing pandemic.

4006 Background: Tivantinib (T) is a selective, oral inhibitor of c-Met, the tyrosine kinase receptor for hepatocyte growth factor involved in tumor cell migration, invasion, proliferation and angiogenesis. T has shown promising results in HCC in phase 1 studies as monotherapy and in combination with sorafenib. Methods: This multi-center RCT, enrolled pts with unresectable HCC, 1 failed systemic therapy, ECOG PS <2. Child-Pugh B-C were excluded. Pts were randomized 2:1 to oral T {360 mg bid (A), 240 mg bid (B)} or placebo (P), stratifying by PS and vascular invasion (VI). Treatment continued until disease progression (PD) or unacceptable toxicity. RECIST 1.1 response was evaluated by CT / MRI every 6 weeks. Crossover to open-label T was allowed after PD. Primary endpoint was time to tumor progression (TTP) in the intent-to-treat (ITT) population by central radiology review. Other endpoints included disease control rate (DCR), PFS, OS, efficacy in Met+ (Met ≥ 2+ in >50% of tumor at immunohistochemistry) pts, safety. Results: Characteristics of the 107 enrolled HCC pts (A= 38, B= 33, P= 36) in T/P: 58/28 male; median age 70/68; PS 0 41/21; VI 22/13; Met+ 22/15; Met- 27/13. Dose A was reduced to B in all pts due to G≥3 neutropenia (NEUT) rate. Major TTP, DCR and PFS benefits were obtained in Met+ pts, with preliminary OS trend favoring T (HR=0.47) and no detrimental effect in Met- pts. DCR (95% CI) in T/P was 44 (31-56) / 31(16-48)% for ITT and 50 (28-72) / 20 (4-48)% in Met+ pts. Most common AEs in T were asthenia (26.8%), NEUT (25.4%), low appetite (25.4%); most common drug-related AEs were NEUT (25.4%), anemia (15.5%). Most frequent drug-related serious AE was neutropenic sepsis (4.2%). Efficacy was similar in A / B with less frequent NEUT in B (21.1% / 6.1%). Final OS, PK, biomarker data will be presented. Conclusions: Compared to P, T significantly benefited second-line HCC pts, especially if Met+, with manageable safety profile at 240 mg BID. [Table: see text]