Immune checkpoint inhibitor therapy has become increasingly recognized as a trigger for hemophagocytic lymphohistiocytosis, a life-threatening hyperinflammatory syndrome that may lead to organ failure without timely interventions. Given the rarity of this entity, patients are often misdiagnosed with more common oncologic complications. In the present series, we describe 3 patients with diverse clinical pictures evaluated at hospital admissions, who were ultimately diagnosed with immune checkpoint inhibitor-associated hemophagocytic lymphohistiocytosis. Treatment consisted of dexamethasone combined with an immunosuppressive agent such as anakinra, ruxolitinib, or tocilizumab, with variable clinical responses among patients. These cases highlight the importance of maintaining a high index of suspicion for hemophagocytic lymphohistiocytosis in patients presenting with systemic inflammation during immune checkpoint inhibitor therapy.
Colorectal cancer (CRC) is a prevalent malignancy worldwide, with its immune evasion representing a pivotal barrier to effective immunotherapy. OLR1 is abnormally expressed in a variety of cancers, but its function in the CRC immune microenvironment and the upstream and downstream modulatory mechanisms remain unclear. Based on the TCGA-COAD data set, OLR1 was upregulated in colorectal cancer (CRC) and correlated with CD8+ T-cell infiltration. Functional assays (qRT-PCR, Western blotting, LDH, ELISA, CCK-8, CFSE, colony formation, Transwell, and flow cytometry) confirmed that OLR1 suppressed CD8+ T-cell function and promoted tumor malignancy. GSEA and inhibitor-based functional validation identified key pathways downstream of OLR1. Mechanistically, bioinformatics, RIP, RNA pull-down, MeRIP, and actinomycin D assays revealed that IGF2BP3 stabilized OLR1 mRNA. Rescue experiments further demonstrated that the IGF2BP3/OLR1 axis regulated the aforementioned pathways and CRC immune evasion. OLR1 was upregulated in CRC and negatively associated with CD8+ T-cell infiltration. Knockdown of OLR1 significantly enhanced the antitumor function of CD8+ T cells. Mechanistically, IGF2BP3 stabilized OLR1 mRNA and up-regulated its expression in an m6A modification-dependent manner, thereby activating the PI3K/AKT/mTOR pathway to inhibit the antitumor activity of CD8+ T cells. IGF2BP3 stabilized OLR1 through m6A modification and activated the PI3K/AKT/mTOR pathway, thereby repressing the antitumor activity of CD8+ T cells and promoting immune evasion in CRC.
Immune checkpoint inhibitors (ICI) have revolutionized the treatment of melanoma and renal cell carcinoma (RCC). Immune therapy response outcomes are based on radiographic measurements of cancer sites alone, without considering whether these sites contain a viable tumor that has metastatic potential. We hypothesized that ICI may lead to residual radiographic abnormalities that either contain nonviable tumor or tumor without metastatic potential that could be controlled with local therapy. In this retrospective cohort study, we identified 8 patients with melanoma and 4 with RCC who had an operable residual metastasis after major tumor response to ICI treatment. On the basis of histologic analysis, 10 (83.3%) of the resected samples showed viable tumor while 2 (16.7%) showed no viable tumor cells on pathology. After surgical removal (11), or radiosurgery (1), to the lesion, all patients had no evidence of melanoma or RCC recurrence for the duration of follow-up. Time from definitive treatment to last follow-up was a mean of 5.9 years (1.1-11.9 y). ICI therapy in melanoma and RCC may lead to a response where existing lesions or new lesions either have no viable cancer or lose their metastatic capacity. Surgical removal or local radiation to those lesions with residual cancer can render patients' long-term disease-free without the need for additional systemic therapy. Consideration of local therapy approaches in patients with isolated residual metastatic disease after ICI response is clinically justified.
Immune checkpoint inhibitors (ICIs) have significantly improved outcomes across multiple malignancies but are associated with immune-related adverse events, including colitis. Although generally uncommon, ICI-induced colitis can lead to significant morbidity and treatment interruption, and data on its incidence and risk factors in the Middle East remain limited. We conducted a retrospective study of adult cancer patients treated with ICIs at a tertiary care center between December 2018 and March 2023. Clinical and treatment-related variables were collected, and univariable and multivariable logistic regression analyses were performed to identify predictors of colitis. Among 784 patients, 19 (2.4%) developed ICI-related colitis. Most cases were moderate to severe, and 57.9% required hospitalization, with a median length of stay of 7 days. All patients had advanced disease. Endoscopic evaluation, performed in 42.1% of patients, demonstrated heterogeneous disease distribution. ICI therapy was discontinued in 78.9% of patients and resumed in 36.8%. Corticosteroids were administered in 68.4% of patients, with a response rate of 92.3%; 1 patient required infliximab. One colitis-related death occurred. In univariable analysis, autoimmune disease, CTLA-4 inhibitor exposure, combination immunotherapy, and concurrent targeted therapy were significantly associated with colitis. In multivariable analysis, autoimmune disease (OR=6.10, 95% CI: 1.55-24.08; P=0.010), combination immunotherapy (OR=3.56, 95% CI: 1.09-11.63; P=0.035), and concurrent targeted therapy (OR=3.88, 95% CI: 1.31-11.54; P=0.015) remained independent predictors. ICI-induced colitis is an uncommon but clinically meaningful toxicity, and recognizing patients at higher risk may help guide closer monitoring and improve clinical management.
The mechanism by which immune checkpoint inhibitors (ICI) cause immune-mediated liver injury is unclear. In 2017, the Society for Immunotherapy of Cancer (SITC) published guidelines for managing immunotherapy toxicity. This article aims to compile clinical approaches to cases of hepatotoxicity associated with immunotherapies (ILICI) in a multicenter setting. This will contribute to the literature by providing data from a larger number of patients. This article is important for ILICI clinical management because it enables the continuation of treatment and raises awareness of these immunotherapy side effects. The study included 56 patients from 20 centers. Grade 3–4 hepatic insufficiency occurred in 24 patients (42.9%). Five (8.9%) patients died due to hepatic insufficiency. Liver biopsies of these 5 patients were consistent with ILICI. The median number of treatment cycles before ILICI developed was 5 (minimum: one, maximum: 80). Steroid therapy was administered to all patients except 6. Eighteen patients who were unresponsive to steroids received various second-line treatments. Some patients received various treatments, such as third-, fourth-, and fifth-line treatments, after the second-line treatment. There was no significant correlation between the median number of ICI cycles and serious adverse events (AST, ALT, bilirubin, and hepatic failure) ( P =0.186, P =1.000, P =0.599, and P =0.484). In addition, no significant correlation was observed between grade 3–4 adverse events and ICI treatment in the first versus subsequent lines ( P >0.05). ILICI is a rare but serious condition, so the treatment modalities used are important. We believe raising awareness of ILICI and evaluating second-line treatments used in steroid-refractory cases contributes to the literature by pooling these treatments together.
Photosensitizer-based antibody conjugates can provide tumor-selective phototoxicity by combining receptor-mediated targeting with local light activation. IR700-based near-infrared photoimmunotherapy represents the clinical benchmark for this strategy; however, photosensitizers with alternative cellular trafficking and phototoxic mechanisms remain of interest. We developed and characterized 2 cetuximab-I21 conjugates, cetuximab-I21-2 and cetuximab-I21-3, targeting epidermal growth factor receptor (EGFR)-expressing tumors. The chemical structures and key photophysical properties of the I21 payload-linkers are disclosed in this revision. Both conjugates achieved a drug-to-antibody ratio of 8 and demonstrated strictly light-dependent cytotoxicity in EGFR-positive cells, with IC 50 values of 0.051-1.093 μg/mL in A431 cells and no detectable dark toxicity. EGFR-low cells showed >400-fold reduced sensitivity, supporting receptor-dependent selectivity. Mechanistic studies revealed receptor-mediated internalization and endolysosomal trafficking, with peak lysosomal colocalization at 3 hours (Pearson r =0.81), followed by mitochondrial membrane depolarization and dose-dependent apoptosis-associated cell death. In vivo fluorescence imaging demonstrated tumor-selective accumulation with sustained retention through 96 hours. In A431 xenografts, cetuximab-I21-3 with triple irradiation (200 J/cm 2 ×3) achieved 50.42% tumor growth inhibition ( P =0.0002). These findings establish cetuximab-I21 as a light-activated, EGFR-targeted antibody-photosensitizer conjugate with a mechanism distinct from that of canonical IR700-based NIR-PIT. Direct IR700 comparison, immune activation studies, photosafety evaluation, and light-dose optimization will be required to define its translational potential.
To investigate the clinical profile of nivolumab-induced autoimmune hemolytic anemia (AIHA) and to reveal the diagnostic and therapeutic patterns of this disease. Articles on nivolumab-induced AIHA published before October 31, 2025 were included. Clinical data were collected for retrospective analysis. A total of 29 patients were included, with a median age of 67 years (range: 18, 89). AIHA occurred at a median of 57 days (range: 6, 390) following initial nivolumab administration, with a median treatment cycle of 3 cycles (range: 1, 39). Fatigue (76.9%) and dyspnea (53.8%) were the predominant clinical manifestations. The laboratory analysis indicated that the median concentrations of hemoglobin and lactate dehydrogenase were 6.2 g/dL (range: 3.5, 8.7) and 710.5 U/L (range: 200, 1574), respectively. Direct antiglobulin test (DAT) results were seronegative in 10.3% and seropositive in 89.7%. Following nivolumab discontinuation and administration of systemic steroids, immunosuppressants, and transfusion support, 89.7% of patients achieved remission. AIHA is a rare and fatal event of nivolumab. DAT may yield negative results in some cases. Warm AIHA is the most common type of nivolumab-induced AIHA. Systemic steroids are the first-line option for AIHA. Refractory AIHA and cAIHA require additional immunosuppressive therapy.
Nutritional status has been associated with prognosis in several cancers. We investigated whether baseline prognostic nutritional index (PNI) and geriatric nutritional risk index (GNRI) as well as their variations during treatment predicted response and survival in extensive-stage small cell lung cancer (ES-SCLC) patients treated with atezolizumab plus chemotherapy. In this multicenter study, records of ES-SCLC patients who received first-line atezolizumab plus platinum-etoposide combination were reviewed retrospectively. Baseline PNI <45 and GNRI <98 were accepted as low. They were reassessed on day 1 of the third cycle to calculate changes from the baseline (ΔPNI and ΔGNRI). Regression models were used to determine predictive factors for response, progression-free and overall survival (PFS and OS). The study included 145 patients. High baseline PNI was independently associated with objective response (odds ratio=2.50, P=0.02). In patients with a low baseline PNI, median PFS was significantly shorter (6.1 vs. 8.7 mo, P=0.04) and it significantly predicted PFS (hazard ratio=1.52, P=0.03). Median OS was significantly shorter in patients with ΔPNI ≤-10% (11.1 vs. 14.9 mo, P=0.01), which independently predicted OS (hazard ratio=2.10, P=0.001). Baseline GNRI and ΔGNRI were not associated with efficacy. However, in patients 65 years of age or older, median PFS was significantly shorter in cases with a low baseline GNRI (7.1 vs. 10.7 mo, P=0.04). PNI and its variations as convenient and cost-effective markers can help predict response and prognosis in ES-SCLC patients receiving first-line atezolizumab plus chemotherapy. GNRI might emerge as an additional prognostic tool in patients 65 years of age or older.
Liver cancer is the most frequent fatal malignancy, and existing treatments have limited efficacy. Tumor necrosis factor receptor superfamily member 12A (FN14) is highly expressed in liver cancer cells and promotes tumor cell proliferation, migration, invasion, and angiogenesis, suggesting that FN14 is a suitable therapeutic target for liver cancer. As a targeted therapy, chimeric antigen receptor T (CAR-T) cells have demonstrated potential for treating solid cancers. We designed a CAR targeting FN14 based on the extracellular domain of tumor necrosis factor superfamily member 12 (TWEAK), the only natural ligand for FN14, and tested its cytotoxic effect on tumor cells in vitro and in vivo. The results show that multiple liver cancer cell lines exhibit high FN14 expression. TWEAK-CAR-T cells specifically and effectively kill these cells in vitro. TWEAK-CAR-T cells also significantly suppress the growth of SK-Hep1 xenografts with high T-cell infiltration in the tumor. Moreover, potent and broad cytotoxicity of TWEAK-CAR-T was observed against diverse tumor cell lines from multiple cancer types. Our findings indicated that TWEAK-CAR-T cell therapy may be an effective therapeutic strategy for liver cancer.
Talimogene laherparepvec (T-VEC) is an intralesional oncolytic viral therapy approved for unresectable melanoma; however, its use is generally contraindicated in immunosuppressed patients, including those receiving systemic corticosteroids. Data regarding the safety and efficacy of T-VEC in patients on physiological steroid replacement for immune checkpoint inhibitor (ICI)-induced adrenal insufficiency is limited. We report the case of a 78-year-old man with recurrent in-transit melanoma of the scalp who developed secondary adrenal insufficiency following pembrolizumab therapy requiring chronic hydrocortisone replacement. Despite ongoing physiological corticosteroid therapy, the patient was treated with intralesional T-VEC and achieved a complete clinical and histologic response without infectious complications. He tolerated treatment well, requiring stress-dose steroids only during intercurrent illness, and remains without evidence of disease at follow-up. This case suggests that physiological corticosteroid replacement may not significantly impair T-VEC efficacy or increase infectious risk. Verbal informed consent was obtained from the patient for publication of this case report and accompanying images.
To examine the clinical characteristics of sintilimab-induced myocarditis and to provide evidence for its diagnosis and management. Retrospective analysis was conducted on clinical case reports of sintilimab-induced myocarditis documented before July 31, 2025. A total of 34 patients were included, with a median age of 64 years (range: 33-85), including 23 (67.6%) male cases. The onset of myocarditis ranged from 1 to 120 days post-treatment, with a median onset of 21 days. The primary clinical presentations included dyspnea (41.2%), chest tightness (35.3%), palpitations (17.6%), and shortness of breath (14.7%), with some cases remaining asymptomatic (8.8%). Comorbid immune-related adverse events included myasthenia gravis (44.1%), myositis (17.6%), and hepatitis (17.6%). Laboratory findings often revealed elevated cardiac troponin I, N-terminal probrain natriuretic peptide, creatine kinase MB, and lactate dehydrogenase. The electrocardiogram mainly showed atrioventricular block (41.2%), ST-T segment changes (44.1%), and atrial or ventricular arrhythmias (50.0%). Echocardiography examination can show normal (34.5%), left ventricular diastolic dysfunction (31.0%), left atrial enlargement (13.8%), and pericardial effusion (13.8%). Cardiac magnetic resonance imaging may show normal (42.9%), myocardial edema (28.6%), and delayed myocardial enhancement (28.6%). Coronary angiography showed normal (73.3%) and coronary artery stenosis of the lumen (26.7%). All patients discontinued sintilimab and received steroid and intravenous immunoglobulin treatment. Outcomes indicated that 79.4% recovered from myocarditis, while 20.6% succumbed. Sintilimab-induced myocarditis has nonspecific manifestations and a high mortality rate. Myasthenia gravis and myositis can occur simultaneously with myocarditis. During simtimab treatment, it is necessary to closely monitor cardiac parameters and symptoms.
The fourth leading cause of cancer death worldwide, hepatocellular carcinoma, is known to progress relentlessly and recur despite treatment. Given the high tumor mutational burden, hepatocellular carcinoma is an attractive target for immunotherapy. Early trials of systemic checkpoint inhibitors have produced promising results, although complete and durable immunologic tumor eradication remains elusive. Pulsed electrical field ablation is a nonthermal ablation technology that causes apoptosis of diseased cells, while preserving the neoantigens for subsequent immune recognition by antigen-presenting cells and effectors. The neoantigens are released when the membrane is permeabilized. Furthermore, pulsed electrical field ablation was shown to induce the formation of tertiary lymphoid structures, congregations of immune cells that form inside the tumor at the ablation site, analogous to a lymph node. We present a novel treatment regimen with pulsed electrical field ablation combined with intratumoral immunotherapy injection. Treatments were performed using computed tomography guidance in a percutaneous manner. Pulsed electrical field ablation was performed within the tumor using the Aliya pulsed electrical field system (Galvanize, Redwood City, CA). After ablation was performed, the immunotherapy was administered into the tumor, mixed with iodinated contrast for visibility and gelfoam slurry for local retention. Three patients underwent treatment, and all treated tumors responded favorably with a decrease in size and a marked decrease in postcontrast enhancement. There were no treatment-related complications or high-grade toxicities. Pulsed electrical field ablation plus intratumoral immunotherapy may be safe and effective for the treatment of advanced hepatocellular carcinoma.
Adoptive transfer of tumor-infiltrating lymphocytes (TILs) achieves promising clinical results in solid tumors. TIL trials use surgically resected tissue to isolate TILs. However, certain tissues are difficult to surgically resect, and a minimally invasive approach might be advantageous if it could achieve similar TIL yields. We tested a minimally invasive approach to culture and expand TILs using endoscopic biopsy tumors from patients with metastatic gastric cancer (GC). TILs were successfully cultured from all of the intestinal GC biopsies, while TIL populations had slow growth from diffuse GCs. Initial TIL growth was faster in intestinal GC biopsies (n=9) than in diffuse GC biopsies (n=4) ( P =0.021). All 4 biopsy TILs tested were expanded >10 10 by our rapid expansion protocol. Biopsy TILs demonstrated equivalent expansion and FACS profiles to TILs cultured from gastrectomy. Thus, clinical-grade TILs can be successfully cultured and expanded from endoscopic biopsy tumors in patients with metastatic GC.
Patients with resectable stage III-IV melanoma are at high risk of recurrence following surgical excision. Neoadjuvant therapy (NEO) with immune checkpoint inhibition (ICI) improves event-free survival and may allow for pathologic treatment response assessment with potential adjuvant therapy de-escalation. Identification of a biomarker correlated with tumor response could facilitate individualized therapeutic decision-making. This study investigates the utility of circulating tumor DNA (ctDNA) as a predictive biomarker of pathologic response in melanoma treated with NEO ICI. We identified melanoma patients treated with NEO ICI at Dana-Farber Cancer Institute and measured personalized ctDNA plasma levels pretreatment, before each NEO ICI cycle, and postoperatively. We evaluated whether ctDNA levels during the NEO course correlated with graded pathologic response. Of 18 patients who underwent NEO ICI, there were 10 pathologic complete responses (pCR; 0% viable tumor), 1 pathologic near-complete response (near pCR; >0% but ≤10% viable tumor), 1 partial response (pPR; >10%-≤50% viable tumor), and 6 nonresponses (pNR; >50% viable tumor). Responders (pCR, near pCR, or pPR) were more likely to have negative presurgical ctDNA levels (100% (12/12) vs. 33% (2/6), P =0.005). In addition to absolute levels, ctDNA kinetics during NEO ICI were also predictive of pathologic response, with nonresponders more likely to show an increase in ctDNA levels between the first and final ICI cycles compared with responders (mean change ctDNA (SD), 0.09 (0.15) vs. -1.16 (3.31), P =0.004). These findings underscore the potential of ctDNA as a dynamic biomarker to inform response-driven, personalized treatment strategies following NEO ICI.
The mechanism by which immune checkpoint inhibitors (ICI) cause immune-mediated liver injury is unclear. In 2017, the Society for Immunotherapy of Cancer (SITC) published guidelines for managing immunotherapy toxicity. This article aims to compile clinical approaches to cases of hepatotoxicity associated with immunotherapies (ILICI) in a multicenter setting. This will contribute to the literature by providing data from a larger number of patients. This article is important for ILICI clinical management because it enables the continuation of treatment and raises awareness of these immunotherapy side effects. The study included 56 patients from 20 centers. Grade 3-4 hepatic insufficiency occurred in 24 patients (42.9%). Five (8.9%) patients died due to hepatic insufficiency. Liver biopsies of these 5 patients were consistent with ILICI. The median number of treatment cycles before ILICI developed was 5 (minimum: one, maximum: 80). Steroid therapy was administered to all patients except 6. Eighteen patients who were unresponsive to steroids received various second-line treatments. Some patients received various treatments, such as third-, fourth-, and fifth-line treatments, after the second-line treatment. There was no significant correlation between the median number of ICI cycles and serious adverse events (AST, ALT, bilirubin, and hepatic failure) ( P =0.186, P =1.000, P =0.599, and P =0.484). In addition, no significant correlation was observed between grade 3-4 adverse events and ICI treatment in the first versus subsequent lines ( P >0.05). ILICI is a rare but serious condition, so the treatment modalities used are important. We believe raising awareness of ILICI and evaluating second-line treatments used in steroid-refractory cases contributes to the literature by pooling these treatments together.
The advent of immune checkpoint inhibitors (ICIs) has transformed the treatment landscape of various malignancies. While these therapies have demonstrated significant efficacy, they are often accompanied by immune-related adverse events (irAEs). Among these, hematologic immune-related toxicities are notably rare. Here, we describe 2 cases of immunotherapy-associated autoimmune hemolytic anemia (ir-AIHA) following the use of programmed cell death 1 (PD-1) ICIs in patients with locally advanced melanoma and cervical cancer. With the increasing use of ICIs, it is essential for physicians to maintain a high index of clinical suspicion for this rare but serious irAE, ensuring timely diagnosis and effective management to optimize patient outcomes.
Immunotherapy has revolutionized endometrial cancer (EC) treatment; our objectives were to characterize immune-related adverse events (irAE) among EC patients and to identify factors associated with risk for irAE. Patients who received pembrolizumab alone or as part of combination therapy for advanced/recurrent EC from 2014 to 2025 were identified. Baseline demographics and cancer characteristics were collected. Potential immune-related adverse events were collected and graded for the cohort. Multiple logistic regression was then performed. A total of 180 patients were included. The mean age was 63.9 years. Black patients comprised 30.6% of the cohort. Endometrioid was the commonest histologic subtype (38.7%), and most tumors (67.7%) were MMR proficient. Ninety-five patients (52.8%) had any-grade irAE, and 14 (7.8%) experienced serious (grades 3-4) irAE. Hypothyroidism was the most common irAE overall (n = 37; 20.6%,) followed by fatigue (n = 23; 12.8%) and diarrhea (n = 20; 11.1%). The most common serious irAEs were diarrhea (n = 4; 2.2%,) followed by hepatitis, dermatitis, and pneumonitis (each n = 3; 1.7%). On univariate analysis, older age, uninsured status, and receipt of pembrolizumab with lenvatinib were associated with any-grade irAE (all P <0.05). In our multiple logistic regression model, uninsured status was an independent predictor of both any-grade irAE (aOR: 5.49; 95% CI: 1.03-29.2) and serious irAE (aOR: 7.96; 95% CI: 1.44-43.9). Receiving pembrolizumab with lenvatinib was independently associated with any-grade irAE (aOR: 7.13; 95% CI: 2.92-17.4). Uninsured status and coadministration with lenvatinib may increase the risk for pembrolizumab-associated irAE among patients with EC. Further collection of real-world data, including unexplored social and economic factors and novel biomarkers, may predict irAE and ultimately help guide clinical decision-making.
This single-center, retrospective real-world study investigated the effectiveness and safety of sugemalimab-based rechallenge in patients with advanced non-small cell lung cancer who experienced disease progression after prior programmed cell death protein 1 (PD-1) inhibitor therapy. Eligible patients had previously achieved clinical benefit (progression-free survival [PFS] ≥6 mo), an Eastern Cooperative Oncology Group (ECOG) performance status of 0-1, and no actionable driver alterations. Nineteen patients received sugemalimab every 3 weeks as monotherapy or in combination with chemotherapy and/or antiangiogenic agents. The objective response rate was 26.3% (5/19; 95% CI: 9.1-51.2), and the disease control rate was 89.5% (17/19; 95% CI: 66.9-98.7), with a median PFS of 4.4 months. Higher programmed death-ligand 1 (PD-L1) tumor proportion score (TPS) correlated with prolonged PFS (TPS ≥50% vs. TPS <1%: 6.1 vs. 2.8 mo; hazard ratio (HR) 0.4, 95% CI: 0.1-0.8). Hypothyroidism was the most common treatment-related adverse event, while grade 3/4 events were uncommon. These findings indicate measurable activity of sugemalimab-based rechallenge in a pre-enriched population and support prospective validation with biomarker-informed stratification.
Metastatic pituitary neuroendocrine tumors (metPitNETs) are rare neoplasms with limited therapeutic options. Temozolomide is the first-line therapy, but primary or secondary resistance frequently occurs. Immune checkpoint inhibitors (ICIs) are emerging as a promising second-line option; however, clinical experience remains limited. We report the long-term follow-up of a 62-year-old male patient who received pembrolizumab (PBZ) treatment for a silent metPitNET derived from the PIT1 lineage after multiple surgical and radiation therapies and temozolomide failure. PBZ was proposed based on extensive PD-L1 expression by tumor cells. A remarkable clinical, radiologic, and metabolic response was soon observed, progressively leading to complete disease remission after 21 months of treatment, with moderate immune-related adverse events. However, an unexpected rapid neurological deterioration occurred, due to the progression of a pseudotumoral temporal radionecrosis surrounded by an impressive vasogenic oedema, requiring emergency neurosurgery 7 weeks after PBZ withdrawal. The temporal mass had progressively developed on a previous small temporal metastasis treated through stereotactic radiosurgery, the corresponding area was hypometabolic at 18 FDG PET-CT imaging, and histopathologic examination confirmed extensive radionecrosis and the absence of residual tumor cells. This is the first documented complete response to ICI in a PIT1-derived metPitNET. However, this remarkable response was complicated by the severe evolution of a brain radionecrosis, probably favoured by long-term PBZ. This case underscores the need for multidisciplinary expertise to differentiate treatment effects from neoplastic progression and to carefully follow-up the patients for potentially severe late treatment-related complications. It also questions the optimal duration of treatment in responsive cases.
This study aimed to assess factors associated with overall survival (OS) in patients with microsatellite stable (MSS) stage IV rectal cancer treated with immunotherapy. In this retrospective review of the NCDB (2015-2021), patients with MSS stage IV rectal adenocarcinoma were divided into immunotherapy and control groups, and propensity-score matched and compared. Multivariable Cox regression analysis was performed to assess the effect of immunotherapy and KRAS genotype on OS. Of 6489 included patients (64.6% males), immunotherapy was given to 47.9%. After matching for age, insurance type, liver metastases, surgery, radiation therapy, and chemotherapy, there were 2422 patients in each group. In the matched cohort, immunotherapy was associated with a similar median OS to the control group [31.8 (95% CI: 27.8-32.2) months vs 29.7 (95% CI: 27.8-32.2) months, P = 0.062]. Immunotherapy was not independently associated with improved OS (HR: 0.88, 95% CI: 0.69-1.14, P = 0.341) but was associated with longer median OS in black patients (25.8 vs 19.1 mo, P = 0.019), patients with bone metastases (22.1 vs 10.7, P < 0.001) and with KRAS mutation (27.4 vs 24.3 mo, P = 0.003). There was no survival benefit from immunotherapy when combined with radical resection, radiation therapy, or chemotherapy. In conclusion, immunotherapy was associated with a modest increase in OS of MSS stage IV rectal cancers, but not independently associated with improved survival. Black patients with bone metastases and KRAS mutations may have survival benefit from immunotherapy. Increased OS with immunotherapy was noted only in patients who did not have surgery, radiation, or chemotherapy. These results seem somewhat disappointing given the enthusiasm for immunotherapy.
