A patient with a PD-L1-negative, TMB-low, KEAP1/STK11 co-mutated metastatic non-small cell lung cancer (NSCLC) experienced a multisite radiological progression at 3 months after initiation of chemoimmunotherapy as first-line treatment for metastatic disease. After the radiological progression, while she was not undergoing treatment, the patient had spontaneous lesions shrinkage and further achieved a prolonged complete response. Genomic and transcriptomic data collected at baseline and at the time of pseudoprogression allowed us to biologically characterize this rare response pattern. We observed the presence of a tumor-specific T-cell response against tumor-specific neoantigens (TNAs). Endogenous retroviruses (ERVs) expression following chemoimmunotherapy was also observed, concurrent with biological features of an anti-viral-like innate immune response with type I IFN signaling and production of CXCR3-associated chemokines. This is the first biological characterization of a NSCLC pseudoprogression under chemoimmunotherapy followed by a prolonged complete response in a PD-L1-negative, TMB-low, KEAP1/STK11 co-mutated NSCLC. These clinical and biological data underline that even patients with multiple factors of resistance to immune checkpoint inhibitors could trigger a tumor-specific immune response to tumor neoantigen, leading to complete eradication of the tumor and probably a vaccinal immune response.

Pseudoprogression of malignancy in patients treated with systemic immunotherapy is a well- recognised phenomenon and has also been seen in patients treated with combined chemoimmunotherapy. Neoadjuvant chemoimmunotherapy prior to surgery is a relatively new treatment strategy for the management of many malignancies. We report the case of a patient who was suspected to have primary lung squamous cell carcinoma progression following neoadjuvant chemoimmunotherapy. Tissue histopathology from biopsies demonstrated granulomatous sarcoid-like inflammation rather than progression or metastatic disease. The patient proceeded to have successful surgical clearance of residual tumour. Significantly, failure to suspect granulomatous reactions and pseudoprogression has profound influence on the trajectory of patient care, such as, the potential for patients to miss out on curative surgery. In this case report and review of the literature, we evaluate the role of pseudoprogression and the need for radiologists to be aware of this phenomenon so that they do not mistakenly report new metastases and derail the treatment paradigm for patients with curable malignant conditions.

Patients with challenging hematological malignancies like classic Hodgkin lymphoma (cHL) can be further complicated when affected by a concurrent coronavirus disease-2019 (COVID-19) infection and often face unique and complex management and outcomes. In this case report, we describe a refractory or relapsed classic Hodgkin lymphoma patient with a recurrent infection of COVID-19 three times preceding chemotherapy. A 52-year-old female presented to our hospital with a second incidence of COVID-19 and a complaint of fever, anorexia, night sweats, and abdominal lymphadenopathy, for which she was diagnosed with mixed cellularity classic Hodgkin lymphoma. Three weeks later, in consideration of her manifestation of lung disease, which was due to her past medical history of airway hypersensitivity and abnormal pulmonary function test along with testing positive for COVID-19, she was started with the first-line chemotherapy of the brentuximab vedotin, doxorubicin, vinblastine, and dacarbazine chemotherapy regimen, commonly referred to as Bv-AVD, without bleomycin. After six cycles of chemotherapy, at the end of treatment, positron emission tomography/computed tomography (PET/CT) revealed the progression of nodes in the abdomen and the development of new lymphadenopathy in the chest and right supraclavicular region. Hence, it was considered refractory Hodgkin\'s lymphoma, and the patient was referred for salvage therapy. She was started on salvage chemotherapy with brentuximab/bendamustine (BvB). Follow-up evaluations after two cycles of BvB continued to show newer lesions in the right sub-diaphragmatic area, internal mammary, and supraclavicular lymph nodes. Therefore, the patient was switched to pembrolizumab immunotherapy, a PD-1 inhibitor. After four cycles of pembrolizumab monotherapy, PET/CT showed significant improvement with a complete molecular response (CMR). Then, she was admitted for high-dose therapy/autologous stem cell transplantation (HDT/ASCT) after collecting stem cells. PET/CT: three months post-ASCT, she continued to be in a CMR with a Deauville score of 1. The patient was continued on pembrolizumab maintenance for six months afterward. Currently, the patient is healthy and doing well. COVID-19 patients with hematological malignancies may experience compromised viral elimination and a prolonged period of viral infection, which may also worsen the symptoms and outcomes and entitle them to comprehensive and extended care.

BACKGROUND: In recent years, neoadjuvant immunotherapy with chemotherapy has shown increasing promise for locally advanced non-small cell lung cancer (NSCLC). However, to establish its clinical efficacy and safety, it is imperative to amass more real-world clinical data. This retrospective study aims to assess the safety and effectiveness of combing sintilimab, a PD-1 inhibitor, with chemotherapy as a neoadjuvant treatment modality in patients diagnosed with potentially resectable NSCLC.
METHODS: We retrospectively reviewed patients with stage II-III NSCLC receiving neoadjuvant chemoimmunotherapy in Sichuan Cancer Hospital between February 2021 and February 2023. Sintilimab injection (intravenously,200 mg, iv, d1, q3w) and platinum-based chemotherapy were administered intravenously every 3 weeks, with radical lung cancer resection planned approximately 4-11 weeks after the last dose. The primary endpoint of the study was pathologic complete response (pCR). The secondary endpoints were objective response rate (ORR), and safety.
RESULTS: Thirteen patients were enrolled, they were mostly diagnosed with stage III NSCLC (IIB 15.4% IIIA 38.5%; IIIB 46.2%). Most of them had pathologically confirmed squamous cell carcinoma (69.2%). All patients received sintilimab combined with platinum-based chemotherapy for 2 to 4 cycles. Notably, none of the patients necessitated a reduction in initial dosages or treatment postponement due to intolerable adverse events. Then, all of them underwent surgical operation. Impressively, nine patients (69.2%) achieved a pathologic complete response. The objective response rate (ORR) stood at 46.15%. Nine patients experienced neoadjuvant treatment-related adverse events (TRAEs), with only one patient (7.6%) encountering a grade 4 neoadjuvant TRAE.
CONCLUSIONS: Therefore, the current study suggested that neoadjuvant sintilimab plus platinum-based chemotherapy can be a safe approach in increasing the efficiency of treatment and hopefully improving the prognosis of patients with potentially resectable locally advanced NSCLC.

Mismatch repair (MMR) deficiency is a fundamental factor affecting the management treatment outcomes of colorectal cancer (CRC). MMR status can be diagnosed by both immunohistochemistry (IHC) polymerase chain reaction (PCR). Since tumors with MMR deficiency are prone to respond to immunotherapy immune checkpoint inhibitors are used to treat such tumors.
A 69-year-old male patient presented to an outside clinic with weight loss and abdominal pain. Radiological investigations detected a mesenteric mass of 10 cm, peritoneal implants, and mediastinal lymphadenopathy. The eventual biopsy result from the mesenteric mass was mucinous adenocarcinoma with a goblet cell pattern. Since the IHC result was unclear for deficiency in mismatch repair (dMMR) metastatic CRC (mCRC), the diagnosis was confirmed with PCR. The patient received 8 cycles of FOLFIRINOX + bevacizumab followed by FOLFOX combined with pembrolizumab. No adverse effect was reported related to immunotherapy which resulted in radiologic and metabolic regression. The patient underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). The final pathology results revealed a pathological complete response and R0 resection. In the 6th month follow-up, no recurrence or metastasis was reported.
Chemotherapy and immunotherapy combination is a promising treatment modality which can also be used for mCRC. This is the index case who received chemotherapy in combination with immunotherapy for mucinous adenocarcinoma of the colon with a goblet cell pattern and had pCR.

Therapeutic options for non-small cell lung cancer (NSCLC) have changed with the introduction of immune checkpoint inhibitors. Immunotherapy is generally well tolerated, but can also be associated with severe adverse events, such as the development of new autoimmune diseases. In patients without a history of autoimmune diseases, psoriasis caused by immunotherapy treatment is rarely described in the literature. The present study describes the case of a 68-year-old man with metastatic NSCLC that started chemoimmunotherapy with carboplatin plus pemetrexed plus pembrolizumab. After two cycles of therapy, the patient developed a G3 maculopapular rash. Biopsy confirmed psoriasis and pembrolizumab treatment was discontinued. At the last follow up, the patient was still on maintenance therapy with pemetrexed alone, which is well tolerated. Psoriasis has rarely been reported as an immune-related adverse event. Although the patient had to stop the immunotherapy treatment, the patient is still exhibiting a response to it. Notably, it has previously been described how skin toxicities are associated with a better outcome. Other studies need to be conducted to identify the risk and predictive factors associated with severe immune adverse events and objective response.

Large-cell neuroendocrine carcinomas (LCNECs), categorized as high-grade neuroendocrine carcinomas, account for approximately 3% of resected lung cancers. LCNECs containing other components are called \'combined LCNECs\' and have no standard treatment. A 73-year-old male with a metastatic brain tumour from a combined LCNEC of the lung containing adenocarcinoma and sarcomatoid components was referred to our department. The patient was treated with chemotherapy consisting of carboplatin and nanoparticle albumin-bound (nab)-paclitaxel in combination with atezolizumab, which was decided in accordance with the histological evaluation of the components. This treatment resulted in partial response and remained durable for 12 months with an ongoing regimen. The current case suggests that the constituents of chemoimmunotherapy should be selected in accordance with the reported efficacy of relevant regimens for each component of the combined LCNEC.

Aim: The emergence of antitumor immunotherapy has been beneficial for patients with tumors, but more attention should be paid to the toxic side effects of chemoimmunotherapy. Here we describe a patient with NK/T-cell lymphoma who developed toxic epidermal necrolysis (TEN) during treatment with a regimen consisting of sintilimab combined with pegaspargase, gemcitabine and oxaliplatin (P-GemOx). Case presentation: A patient received six cycles of P-GemOx chemotherapy as first-line treatment; 1 year later, he received the same dose of P-GemOx combined with sintilimab as chemoimmunotherapy due to recurrence of NK/T-cell lymphoma. He developed a massive rash that quickly developed into TEN after the fourth chemoimmunotherapy. Conclusion: Although rare, cases of fatal TEN caused by single-agent PD-1 inhibitor or gemcitabine have been reported. Careful attention to drug-related cutaneous toxicities is needed when these two agents are combined. This report highlights the significance of TEN as a rapid and serious adverse event induced by chemoimmunotherapy.
Immune checkpoint inhibitors that block the interaction of PD-1 with its ligand, PD-L1, have been increasingly used in cancer therapy. However, some rare side effects induced by these drugs, such as toxic epidermal necrolysis (TEN), can be extremely dangerous. Here we describe a patient with natural killer/T-cell lymphoma who developed TEN during treatment with a combination of sintilimab and pegaspargase/gemcitabine/oxaliplatin (P-GemOx). The patient received six cycles of P-GemOx chemotherapy as first-line treatment and showed no skin reactions during or after treatment. However, 1 year later, the patient received the same dose of P-GemOx combined with sintilimab as second-line treatment for recurrent natural killer/T-cell lymphoma and developed a massive rash that quickly developed into TEN after four cycles of chemoimmunotherapy. Cutaneous toxicities are some of the most prevalent immune-related adverse events, both with anti-PD-1 and anti-PD-L1 agents, which correspond to a class effect.

Gastric mucosa-associated lymphoid tissue (MALT) lymphoma is a form of low-grade B cell lymphoma that is associated with Helicobacter pylori (H. pylori) infection and has a generally favorable prognosis. It tends to remain localized for extended periods before dissemination to other body parts. H. pylori eradication therapy is essential in all gastric MALT lymphoma patients regardless of the disease stage. However, no conclusive treatment regimen for gastric MALT lymphoma with central nervous system (CNS) involvement has been established to date. Herein we present a case of a gastric MALT lymphoma patient with CNS involvement who was successfully treated via combination chemoimmunotherapy and intrathecal chemotherapy. A 53-year-old woman was diagnosed with stage IV gastric MALT lymphoma with CNS involvement in 2012. She underwent 6 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone), 2 cycles of rituximab, and 10 cycles of intrathecal chemotherapy. Six months later, radiological testing revealed no evidence of disease. In 2019 a mass was discovered in her right parietal lobe. She again underwent 6 R-CHOP cycles and 8 intrathecal chemotherapy cycles. The patient is being actively followed without any evidence of recurrence. Based on this successful case, chemoimmunotherapy combined with intrathecal chemotherapy could possibly be used for the treatment of gastric MALT lymphoma with CNS involvement.

Primary Epstein-Barr-Virus (EBV)-associated pulmonary lymphoepithelioma-like carcinoma (LELC) is an aggressive rare cancer. Higher incidences have been observed in Asian sub-populations. Multimodal treatment paradigms have emerged as promising novel strategies in the management of advanced NSCLC. In this report, we describe the case of a 34-year-old female patient of Asian origin with a post-partum initial diagnosis of pulmonary LELC. Multimodal treatment with chemoimmunotherapy and hypofractionated irradiation to the primary tumour and main metastatic sites led to a favourable response demonstrating that radiotherapy may potentially augment anti-tumour immunity. To the best of our knowledge, this is the first case report on this novel therapy strategy of multi-site hypofractionated radiotherapy and chemoimmunotherapy for metastatic pulmonary EBV-associated LELC.