Lung cancer is the leading cause of cancer-related deaths worldwide. Patients with resectable NSCLC are often treated with surgery and adjuvant chemotherapy. However, these patients continue to have a high risk of recurrence and death. Unfortunately, there has been little progress in the treatment of resectable NSCLC over the past several decades. Neoadjuvant therapy, which has been considered as an approach to improve survival in patients with resectable NSCLC, is a hotly debated topic. A systematic review of 32 randomized trials involving 10,000 patients revealed that there was no difference in survival between preoperative and postoperative chemotherapy. Because of such results and the theoretical concern about resectable tumors progressing on relatively ineffective neoadjuvant chemotherapy, and thus becoming unresectable, neoadjuvant chemotherapy fell out of favor, and many clinicians preferred adjuvant chemotherapy after surgery. However, neoadjuvant therapy has been revived in the past couple of years, with emerging data from various ongoing trials suggesting that neoadjuvant immunotherapy may have significant efficacy and could potentially improve the survival of patients with resectable NSCLC. In this review article, we discuss the evidence supporting the role of neoadjuvant immunotherapy in the multimodal management of resectable NSCLC. We summarize early results of ongoing clinical trials and highlight the challenges in adopting a uniform definition of treatment "success." We address hurdles to be overcome for seeking regulatory approval for neoadjuvant immunotherapy and establishing it as a standard of care. Finally, we provide some perspectives for the future.

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This article reports a rare case of the use of low-dose ketamine infusion as an adjuvant to opioids to treat pain in sickle cell disease. A 31-year-old African-American male with history of sickle cell disease presented to the emergency department with complaints of chest tightness, multiple joint pain, and headache for 1 week. His vital signs and physical examination were unremarkable. His admission lab included hemoglobin of 8.4 g/dl, reticulocyte count of 16.3%, bilirubin of 1.7 mg/dl, and LDH of 1,267 U/l. Chest X-ray showed middle and lower lobe opacity and interstitial thickening. He was treated for acute pain crisis and community-acquired pneumonia with intravenous fluids, supplemental oxygen, and intravenous levofloxacin. He was placed on fentanyl patient-controlled analgesia (PCA), oxycodone, ketorolac, and methadone with co-analgesic gabapentin and venlafaxine. Over the course of his hospitalization, his chest pain resolved, but the joint pains continued. He was then transferred to the ICU and was discharged a day later after 7 days of ketamine infusion. Ketamine is a noncompetitive antagonist at the N-methyl-D-aspartate (NMDA) receptor. This property has been shown to modulate opioid tolerance and opioid-induced hyperalgesia. There have been a very few published reports on the use of low-dose ketamine in sickle cell pain management. A PubMed search revealed four published articles (Table 1). Fourteen out of the 17 cases (82.35%) who received ketamine infusion showed improvement in self-reported pain intensity and significant reduction in opioid dosage. Only one patient (5.9%) developed serious side effect leading to discontinuation of the drug. A low-dose ketamine can be an option for pain control in sickle cell disease. Randomized trial is required to establish this benefit of ketamine over currently available therapies.

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Small cell lung cancer (SCLC) comprises about 15% of all cases of lung cancer. In recent years, owing to a change in the epidemiology of smoking habits, the incidence of the tumor has decreased; however, it remains a significant challenge to global health. While the tumor has a favorable initial response to chemoradiation, relapse is invariable, and second-line regimens may be intolerable given the severity of side effects. For patients with tumors resistant to second-line regimens, no current standard regimens exist. Rovalpituzumab tesirine is a novel antibody-drug conjugate, targeting delta-like protein 3, fundamental in the downstream cellular signaling for proliferation and apoptosis. This drug is reported to have shown promise in pre-clinical and phase I trials. It appears effective in decreasing tumor burden and is reported to be well tolerated, albeit with a significant adverse effect profile. Currently, it is being studied as part of initial and subsequent line chemotherapeutic regimens; it remains to be seen if this is a viable option in the treatment of SCLC. This may add to the agents that can be used against SCLC, and help improve outcomes.