Transformation of G1-G2 neuroendocrine tumors to neuroendocrine carcinomas following peptide receptor radionuclide therapy.

We observed that some patients with well-differentiated neuroendocrine tumors (NET) who received peptide receptor radionuclide therapy (PRRT) with Lutetium-177 (177Lu) DOTATATE developed rapid disease progression with biopsy-proven histologic transformation to neuroendocrine carcinoma (NEC), an outcome that has not been previously described. Therefore, we conducted a retrospective review of all patients with well-differentiated G1-G2 NET who received at least one cycle of PRRT with (177Lu) DOTATATE at our center from January 2019 to December 2020. Among 152 patients, we identified 7 patients whose NET transformed to NEC. Median time from start of PRRT to transformation was 8.2 months (range: 2.6-14.4 months). All patients whose tumors underwent transformation had pancreatic tail as the primary site and had prior chemotherapy with temozolomide. No differences in the incidence of transformation were observed according to gender, race, original tumor grade, or number of prior therapies. Six patients received treatment with platinum and etoposide after transformation with two patients having partial response as best response. All patients with transformation died from progressive disease with median overall survival (OS) after transformation of 3.3 months (95% CI 2.1-4.4). Molecular testing of transformed NEC identified mutation(s) in TP53 and/or ATM in all cases. Transformation of NET to NEC following PRRT is associated with aggressive course and dismal prognosis. Patients with pancreatic tail as the primary site who had prior therapy with temozolomide may be at a higher risk. Further investigation is necessary to determine the best treatment sequence in this patient population.

Decreasing utilization for postoperative radiation therapy in locoregionally advanced medullary thyroid cancer.

BACKGROUND: Use of postoperative radiation therapy (PORT) in locoregionally advanced medullary thyroid cancer (MTC) remains controversial. The objective was to evaluate the effect of PORT on locoregional control (LRC) and overall survival (OS). METHODS: Retrospective cohort study of 346 MTC patients separated into PORT and no-PORT cohorts. Relative indications for PORT, as well as changes in patterns of treatment, were recorded. RESULTS: 49/346 (14%) received PORT. PORT was associated with worse OS; adjusted HR = 2.0 (95%CI 1.3-3.3). PORT was not associated with improved LRC, even when adjusting for advanced stage (Stage III p = 0.892; Stage IV p = 0.101). PORT and targeted therapy were not associated with improved OS compared to targeted therapy alone; adjusted HR = 1.2 (95%CI 0.3-4.1). CONCLUSIONS: Use of PORT in MTC has decreased and its indications have become more selective, coinciding with the advent of effective targeted therapies. Overall, PORT was not associated with improved LRC or OS.

[Value of postoperative radiotherapy and analysis of prognostic factors in early-stage neuroendocrine carcinoma of cervix].

Objective: To evaluate the effect of postoperative radiotherapy and high-risk pathological factors on the prognosis of early-stage neuroendocrine carcinoma of cervix (NECC). Methods: A single-center retrospective cohort study of early-stage NECC in Peking Union Medical College Hospital from January 2011 to April 2022 were enrolled. The patients were treated with radical hysterectomy±adjuvant treatment. They were divided into postoperative non-radiation group and postoperative radiation group. The possible postoperative recurrence risk factors identified by univariate analysis were assessed using multivariate logistic regression. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate. Results: (1) Sixty-two cases were included in the study, including 33 cases in postoperative non-radiation group and 29 cases in postoperative radiation group. (2) The median follow-up time was 37 months (ranged 12-116 months), with 23 cases (37%) experienced recurrences. There were 7 cases (11%) pelvic recurrences and 20 cases (32%) distant recurrences, in which including 4 cases (6%) both pelvic and distant recurrences. Compared with postoperative non-radiation group, the postoperative radiation group had a lower pelvic recurrence rate (18% vs 3%; P=0.074) but without statistic difference, a slightly elevated distant recurrence rate (24% vs 41%; P=0.150) and overall recurrence rate (33% vs 41%; P=0.513) without statistically significances. Univariate analysis showed that lymph-vascular space invasion and the depth of cervical stromal invasion≥1/2 were risk factors for postoperative recurrence (all P<0.05). Multivariate analysis showed lymph-vascular space invasion was an independent predictor for postoperative recurrence (OR=23.03, 95%CI: 3.55-149.39, P=0.001). (3) During the follow-up period, 18 cases (29%, 18/62) died with tumor, with 10 cases (30%, 10/33) in postoperative non-radiation group and 8 cases (28%, 8/29) in postoperative radiation group, without significant difference (P=0.814). The postoperative 3-year and 5-year survival rate was 79.2%, 60.8%. The depth of cervical stromal invasion≥1/2 was more common in postoperative radiation group (27% vs 64%; P=0.011), and postoperative radiation in such patients showed an extended trend in PFS (32.3 vs 53.9 months) and OS (39.4 vs 73.4 months) but without statistic differences (P=0.704, P=0.371). Compared with postoperative non-radiation group, the postoperative radiation did not improve PFS (54.5 vs 37.3 months; P=0.860) and OS (56.2 vs 62.4 months; P=0.550) in patients with lymph-vascular space invasion. Conclusions: Postoperative radiation in early-stage NECC patients has a trend to reduce pelvic recurrence but not appear to decrease distant recurrence and overall recurrence, and has not improved mortality. For patients with the depth of cervical stromal invasion≥1/2, postoperative radiation has a trend of prolonging OS and PFS but without statistic difference. Lymph-vascular space invasion is an independent predictor for postoperative recurrence, but postoperative radiation in such patients does not seem to have any survival benefits.

Striking Size Reduction of Rapidly Growing Pancreatic Neuroendocrine Carcinoma Metastatic Nodal Conglomerate After Only 2 Cycles of 177 Lu-DOTATATE.

ABSTRACT: Peptide receptor radionuclide therapy (PRRT) with 177 Lu-DOTATATE has shown great treatment efficacy in patients with well-differentiated metastatic neuroendocrine tumors and a metastatic size reduction of ~20% for metastatic lesions <3 cm in size. We present a 66-year-old man with pancreatic neuroendocrine carcinoma, who had a rapidly growing metastatic nodal conglomerate, which measured close to 10 cm in size. After only 2 cycles of PRRT with 177 Lu-DOTATATE, the nodal conglomerate had a striking size reduction greater than 75%. This case highlights the potential efficacy of PRRT with 177 Lu-DOTATATE for treatment of aggressive neuroendocrine neoplasms.

Delta-like ligand 3-targeted radioimmunotherapy for neuroendocrine prostate cancer.

Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer with limited meaningful treatment options. NEPC lesions uniquely express delta-like ligand 3 (DLL3) on their cell surface. Taking advantage of DLL3 overexpression, we developed and evaluated lutetium-177 (177Lu)-labeled DLL3-targeting antibody SC16 (177Lu-DTPA-SC16) as a treatment for NEPC. SC16 was functionalized with DTPA-CHX-A" chelator and radiolabeled with 177Lu to produce 177Lu-DTPA-SC16. Specificity and selectivity of 177Lu-DTPA-SC16 were evaluated in vitro and in vivo using NCI-H660 (NEPC, DLL3-positive) and DU145 (adenocarcinoma, DLL3-negative) cells and xenografts. Dose-dependent treatment efficacy and specificity of 177Lu-DTPA-SC16 radionuclide therapy were evaluated in H660 and DU145 xenograft-bearing mice. Safety of the agent was assessed by monitoring hematologic parameters. 177Lu-DTPA-SC16 showed high tumor uptake and specificity in H660 xenografts, with minimal uptake in DU145 xenografts. At all three tested doses of 177Lu-DTPA-SC16 (4.63, 9.25, and 27.75 MBq/mouse), complete responses were observed in H660-bearing mice; 9.25 and 27.75 MBq/mouse doses were curative. Even the lowest tested dose proved curative in five (63%) of eight mice, and recurring tumors could be successfully re-treated at the same dose to achieve complete responses. In DU145 xenografts, 177Lu-DTPA-SC16 therapy did not inhibit tumor growth. Platelets and hematocrit transiently dropped, reaching nadir at 2 to 3 wk. This was out of range only in the highest-dose cohort and quickly recovered to normal range by week 4. Weight loss was observed only in the highest-dose cohort. Therefore, our data demonstrate that 177Lu-DTPA-SC16 is a potent and safe radioimmunotherapeutic agent for testing in humans with NEPC.

Evaluation of Survival and Postoperative Radiation Among Patients with Advanced Medullary Thyroid Carcinoma: An Analysis of the National Cancer Database.

BACKGROUND: This study compared survival between patients who had medullary thyroid cancer (MTC) treated with surgery alone and patients who underwent surgery and radiation (SRT). METHODS: Patients from the National Cancer Database (NCDB) with a diagnosis of stage 3 or 4 MTC, lymph node disease, and no distant metastases between 2008 and 2016 were studied. Kaplan-Meier analyses and log-rank statistics were used to estimate and compare overall survival between patients treated with surgery alone and those treated with SRT. Mutlivariable Cox proportional hazards models and propensity-matching were used to adjust for confounding and selection bias. RESULTS: Among 1370 patients, 1112 (81%) received surgery alone, and 258 (19%) received SRT. The hazard ratio for mortality in the SRT group was 1.784 (95% confidence interval [CI] 1.313-2.43) after multivariable adjustment for confounding variables. Furthermore, SRT remained associated with a higher mortality rate (p < 0.008) after propensity-matching in an effort to adjust for selection bias. CONCLUSIONS: This analysis of NCDB patients showed that SRT is associated with a significantly higher mortality rate among patients treated for stage 3 or 4 IV MTC with positive lymph node disease. Although this observation can be attributed to unmeasured confounders or selection bias, the cause for the profound survival differences deserves prospective evaluation, especially as adjuvant therapies for this disease continue to evolve.

Radiotherapy of sinonasal cancers.

We present the update of the recommendations of the French society of radiotherapy and oncology on the indications and the technical methods of carrying out radiotherapy of sinonasal cancers. Sinonasal cancers (nasal fossae and sinus) account for 3 to 5% of all cancers of the head and neck. They include carcinomas, mucosal melanomas, sarcomas and lymphomas. The management of sinonasal cancers is multidisciplinary but less standardized than that of squamous cell carcinomas of the upper aerodigestive tract. As such, patients with sinonasal tumors can benefit from the expertise of the French expertise network for rare ENT cancers (Refcor). Knowledge of sinonasal tumour characteristics (histology, grade, risk of lymph node involvement, molecular characterization, type of surgery) is critical to the determination of target volumes. An update of multidisciplinary indications and recommendations for radiotherapy in terms of techniques, target volumes and radiotherapy fractionation of the French society of radiotherapy and oncology (SFRO) was reported in this manuscript.

Primary small cell neuroendocrine carcinoma in the nasal cavity: A CARE-compliant case report.

RATIONALE: Small cell neuroendocrine carcinoma of the nasal cavity and paranasal sinuses is a rare but aggressive neoplasm with a poor prognosis and a strong propensity for regional recurrence and distant metastasis. Diagnosis is challenging and relies on immunohistochemical study. Treatment includes surgical resection, radiation therapy, chemotherapy, or a combination of these modalities. However, the optimal therapeutic strategy is still controversial. Due to its rarity, the complexity of the histological diagnosis, and the variety of the treatment regimens, we presented a case of primary small cell neuroendocrine carcinoma in the nasal cavity with description of the clinical manifestation, pathology features, and our treatment regimen. PATIENT CONCERNS: An 82-year-old female patient with hypertension presented with right epistaxis on and off with nasal obstruction for several days. DIAGNOSIS: An exophytic mass over the posterior end of the right inferior turbinate was found on nasopharyngoscope. Biopsy was done and the pathology confirmed small cell carcinoma, strongly positive for cytokeratin (AE1/AE3) and insulinoma-associated protein 1 (INSM-1), scatteredly positive for chromogranin A, synaptophysin and CD56. The final diagnosis was small cell neuroendocrine carcinoma of right nasal cavity, pT1N0M0, stage I. INTERVENTIONS: The patient underwent wide excision of right intra-nasal tumor and post-operative radiotherapy with a dose of 6600 cGy in 33 fractions. OUTCOMES: No local recurrence or distant metastasis was noted during the 12 months of follow-up. LESSONS: Multimodality treatment remains the most common therapeutic strategy, although no proven algorithm has been established due to the rarity of this disease. Further investigation is needed for providing evidence to standardize the treatment protocol.

Successful salvage of recurrent leptomeningeal disease in large cell neuroendocrine lung cancer with stereotactic radiotherapy.

A 70-year old male with stage I large cell neuroendocrine carcinoma (LCNEC) of the lung underwent resection of a metachronous 5 cm brain metastasis and received postoperative hypofractionated stereotactic radiotherapy (hfSRT). Five sequential nodular leptomeningeal metastases up to 5.3 cm in diameter were diagnosed on MRI within 10 months and were treated with SRT. Currently the patient has no evidence of intracranial disease 24 months after last irradiation without chemotherapy or whole brain radiotherapy. This is the first report of sustained complete remission of multiple large leptomeningeal metastases achieved with hfSRT, highlighting this brain-sparing approach in selected patients with LCNEC lung cancer.

Metastatic Medullary Thyroid Cancer: The Role of 68Gallium-DOTA-Somatostatin Analogue PET/CT and Peptide Receptor Radionuclide Therapy.

CONTEXT: Metastatic medullary thyroid cancer (MTC) is a rare malignancy with minimal treatment options. Many, but not all, MTCs express somatostatin receptors. OBJECTIVE: Our aim was to explore the role of 68Ga-DOTA-somatostatin analogue (SSA) positron emission tomography (PET)/computed tomography (CT) in patients with metastatic MTC and to determine their eligibility for peptide receptor radionuclide therapy (PRRT). METHODS: We retrospectively identified patients with metastatic MTC who had 68Ga-DOTA-SSA PET/CT at 5 centers. We collected characteristics on contrast-enhanced CT, 68Ga-DOTA-SSA and 18F-FDG PET/CT. The efficacy of PRRT was explored in a subgroup of patients. Kaplan-Meier analysis was used to estimate time to treatment failure (TTF) and overall survival (OS). RESULTS: Seventy-one patients were included (10 local recurrence, 61 distant disease). Of the patients with distant disease, 16 (26%) had ≥50% of disease sites with tracer avidity greater than background liver, including 10 (10/61, 16%) with >90%. In 19 patients with contemporaneous contrast-enhanced CT, no disease regions were independently identified on 68Ga-DOTA-SSA PET/CT. Thirty-five patients had an 18F-FDG PET/CT, with 18F-FDG positive/68Ga-DOTA-SSA negative metastases identified in 15 (43%). Twenty-one patients had PRRT with a median TTF of 14 months (95% CI 8-25) and a median OS of 63 months (95% CI 21-not reached). Of the entire cohort, the median OS was 323 months (95% CI 152-not reached). Predictors of poorer OS included a short calcitonin doubling-time (≤24 months), strong 18F-FDG avidity, and age ≥60 years. CONCLUSIONS: The prevalence of high tumor avidity on 68Ga-DOTA-SSA PET/CT is low in the setting of metastatic MTC; nevertheless, PRRT may still be a viable treatment option in select patients.

Successful management of small cell neuroendocrine carcinoma of the ureter with neoadjuvant chemotherapy and adjuvant chemoradiation: case report and literature review.

Neuroendocrine tumours (NETs) of the urinary tract are rare, and the urinary bladder is the the most common primary site. Primary ureteric NET is rarer with under 80 cases reported in the literature thus far. Most of these tumours are of the high-grade small cell neuroendocrine carcinoma subtype, which has a worse prognosis. Neoadjuvant chemotherapy has a proven role in the management of NET of the bladder as it downstages the tumour, which may add to significant recurrence-free survival and overall survival. We report the successful management of a patient with locally advanced small cell neuroendocrine carcinoma of the ureter, who had a pathological complete response after neoadjuvant chemotherapy with etoposide and cisplatin. He subsequently received adjuvant chemotherapy followed by radiation and is recurrence-free at a follow-up of 1 year.

Efficacy and safety of peptide receptor radionuclide therapy in advanced radioiodine-refractory differentiated thyroid cancer and metastatic medullary thyroid cancer: a systematic review.

BACKGROUND: It has been shown that a subgroup of patients with differentiated thyroid cancer (DTC) and medullary thyroid carcinoma (MTC) would progress to advanced stages of thyroid cancer. Therefore, the present study was done to systematically review available evidence in order to investigate efficacy and safety of peptide receptor radionuclide therapy (PRRT) in the patients with advanced radioiodine refractory differentiated thyroid cancer (RR-DTC) and metastatic MTC. METHODS: For this purpose, relevant studies investigated safety and efficacy of PRRT in the patients with advanced RR-DTC and metastatic MTC were identified by searching Medline (Pubmed, Ovid, and Ebsco), Scopus, Embase, Web of Science, and Cochrane Library databases (from database inception to March 24, 2021). The review was performed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. Searching was done independently by two investigators. Two researchers independently extracted the data and any disagreement was adjudicated by consensus. Quality of the studies was assessed using the tool of case reports/series in systematic reviews. RESULTS: Among 2284 related papers, 41 papers met the inclusion criteria. A total of 157 patients with RR-DTC were treated with PPRT. Biochemical and objective responses (partial and complete) were observed in 25.3 and 10.5% of patients, respectively. Among 220 patients with metastatic MTC, biochemical and objective responses were observed in 37.2 and 10.6% of the patients, respectively. Forty-six deaths were reported in 95 patients with advanced RR-DTC. In addition, 63 deaths were observed in 144 patients with metastatic MTC. Major side effects were reported in 124 patients treated with 90Y -based agent. In the patients treated with 177Lu-DOTA-TATE and 111In-Octreotide, mild and transient hematologic or renal complications were reported. CONCLUSION: Findings of the study revealed that in the absence of the established treatment for the patients with RR-DTC and metastatic MTC, PRRT could be effective with few adverse events. TRIAL REGISTRATION: PROSPERO registration number: CRD42019125245 .

The role of radiotherapy in neuroendocrine cervical cancer: SEER-based study.

BACKGROUND: There are few randomised prospective data or guidelines for the treatment of neuroendocrine cervical cancer (NECC). In addition, the role of radiotherapy (RT) in NECC remains controversial. We used the Surveillance Epidemiology and End Results (SEER) database to investigate the role of RT for the treatment of NECC. Particular attention was paid to the different role of RT in patients with or without a metastasis (M1 or M0). METHODS: The SEER database was queried for studies on NECC. We limited the year of diagnosis to the years 2000 to 2015. A Pearson's two-sided Chi-squared test, the Kaplan-Meier method and Cox regression analysis models were used for statistical analyses. The overall survival (OS) was studied for the overall group and between-subgroup groups. RESULTS: NECC was an aggressive disease with a mean OS of only 46.3 months (range of 0-196 months, median of 23 months). No significant differences were shown between the surgery (S) and S + RT groups (p = 0.146) in the M0 (without metastasis) arm. However, there was a statistically significant difference in OS between the S and S + RT groups in the M1 (with metastasis) arm (median of 44.6 months for the S group and 80.9 months for the S + RT group), p = 0.004. The mean survival was significantly longer for M0 patients than for M1 patients when treated with S only (S arm), that is, 82.1 months versus 44.6 months, respectively (log-rank p = 0.000). We also noted that when patients received adjuvant RT (S + RT arm), there were no significant differences between the M0 and M1 groups (median of 90.6 and 81.0 months, p = 0.704, respectively). Age at diagnosis, chemotherapy, T stage and N stage were significant factors for OS in the M0 arm. Interestingly, radiotherapy was the only significant factor for OS with a multivariate HR for death of 0.502 (95% CI 0.206-0.750, p = 0.006) in the M1 arm. CONCLUSIONS: RT may be carefully used in patients who are negative for metastases. Using SEER data, we identified a significant survival advantage with the combination of radiotherapy and surgery in NECC with metastases. This suggests that active local treatment should be conducted and has a significant impact on OS, even if a distant metastasis has occurred.

External Beam Radiotherapy for Medullary Thyroid Cancer Following Total or Near-Total Thyroidectomy.

OBJECTIVES: Medullary thyroid carcinoma (MTC) often presents with advanced disease and takes an aggressive course as compared with more well-differentiated thyroid cancers. The role of adjuvant therapy, specifically external beam radiotherapy (EBRT), remains disputed. This study investigated the impact of EBRT on survival in MTC. STUDY DESIGN: Cross-sectional analysis of a national database. SETTING: Patients with MTC were identified from the SEER program (Surveillance, Epidemiology, and End Results). METHODS: Collected variables included age, sex, race, T and N stages, lymph node yield, and use of EBRT. Propensity score matching was performed to determine the association of EBRT with overall and disease-specific survival. RESULTS: A total of 2046 patients with locoregional MTC were identified. Of these, 152 received EBRT. Patients receiving EBRT were older and had more advanced disease. EBRT was not associated with differences in overall survival (hazard ratio, 1.12; 95% CI, 0.76-1.65) or disease-specific survival (1.66; 0.93-2.95), as well as in subset analysis of age and disease extent. Long-term overall survival was similar, with 77.3% (95% CI, 70.1%-85.3%) and 58.3% (48.2%-70.5%) of patients without EBRT alive at 5 and 10 years, respectively (vs 70.7% [63.2%-79.1%] and 52.3% [43.3%-63.2%] of patients with EBRT). There were no differences in 5- and 10-year disease-specific survival. CONCLUSION: EBRT was not associated with improved overall or disease-specific survival in patients with MTC. Decisions regarding EBRT must be made with consideration of morbidity relative to benefit for individual patients.

A Rare Case of Locally Advanced Primary Small Cell Neuroendocrine Carcinoma of the Adrenal Gland.

BACKGROUND/AIM: Primary small cell neuroendocrine carcinoma (SCNEC) of the adrenal gland is extremely rare with limited reports in the literature. There remain no definitive treatment guidelines, largely due to the rarity of the malignancy. CASE REPORT: We present the case of a 62-year-old Caucasian male who presented with low back pain and was found to have a large retroperitoneal mass arising from the left adrenal gland, measuring 18.3 × 12.2 centimeters (cm). Biopsy was consistent with small cell carcinoma/high grade neuroendocrine carcinoma. Staging workup including CT chest and bone scan was negative. The patient was treated with chemotherapy, radiation therapy, and surgery; complete pathological response of the left adrenal tumor was achieved. Surveillance imaging every three months continued to show no evidence of recurrent disease. CONCLUSION: Primary SCNEC of the adrenal gland is rare and lacks standard treatment guidelines. Our case represents a possible treatment approach that may provide better clinical outcomes, however, further investigations are necessary to help define ideal treatment guidelines.

Mediastinal Neuroendocrine Carcinoma Slowly Growing for 8 Years after Surgical Resection of Esophageal Squamous Cell Carcinoma.

A 70-year-old woman was referred to our department due to a solitary mediastinal tumor which gradually grew near the site of anastomosis for 8 years after radical surgery of esophageal squamous cell carcinoma. It was difficult to distinguish the lymph node recurrence of esophageal cancer from another tumor of unknown primary origin. Endoscopic ultrasound-guided fine-needle aspiration was performed, and the tumor was diagnosed to be neuroendocrine carcinoma. She received concurrent chemoradiotherapy with etoposide plus cisplatin. After the completion of chemoradiotherapy, the tumor disappeared. A solitary growing tumor which develops after radical resection of cancer would be better to be examined histologically in order to make an accurate diagnosis and select the most appropriate treatment.

Peptide Receptor Radionuclide Therapy in Patients With Differentiated Thyroid Cancer: A Meta-analysis.

PURPOSE: As patients with progressive medullary thyroid cancer (MTC) and radioiodine-refractory metastatic differentiated nonmedullary thyroid cancer (DTC) have poor prognoses and present therapeutic challenges, peptide receptor radionuclide therapy (PRRT) targeting the somatostatin receptor provides a promising option. This meta-analysis evaluated the therapeutic effects and outcomes of PRRT in differentiated thyroid cancer. PATIENTS AND METHODS: PUBMED, EMBASE, CINAHL, SCOPUS, and COCHRANE were systematically searched using appropriate key words. The primary therapeutic effect was the radiological response after PRRT, and the objective response rate (ORR) and disease control rate (DCR) were identified in MTC and DTC, respectively. The outcome of serious adverse events (grade 3 or 4), additional therapeutic effects of F-FDG PET/CT and biochemical (calcitonin and thyroglobulin) responses, and radionuclides for PRRT were assessed as subgroup analyses. The parameters were generated as pooled proportions. RESULTS: Eleven articles with 165 patients were included (98 patients with MTC and 67 patients with DTC). PRRT achieved pooled proportions of ORR in 8.53% to 15.61%, DCR in 53.95% to 59.99%, and serious adverse events in 2.79% to 2.82% in MTC and DTC patients. F-FDG PET/CT and biochemical responses revealed similar results as the radiological response. Lu-based PRRT (ORR, 11.48%-24.52%; DCR, 61.47%-67.26%) showed better therapeutic effects than Y-based PRRT (ORR, 6.98%-13.82%; DCR, 50.86%-57.29%). CONCLUSIONS: This meta-analysis suggests that PRRT could be a potential and safe strategy for MTC and DTC. In particular, PRRT with Lu exhibited improved therapeutic effects relative to PRRT with Y.

The role of radiotherapy in pulmonary large cell neuroendocrine carcinoma: propensity score matching analysis.

The aim of the study was to investigate the survival advantage of radiotherapy (RT) in patients with pulmonary large cell neuroendocrine carcinoma (LCNEC). Patients with pulmonary LCNEC were extracted from the Surveillance, Epidemiology, and End Results (SEER) dataset between January 2004 and December 2013. Propensity score matching (PSM) analysis with 1:1 was used to ensure well-balanced characteristics of all comparison groups. A total of 1480 eligible cases were identified, with a median follow-up time of 11 months (0-131 months). After PSM, 980 patients were classified in no radiotherapy (No RT) and radiotherapy (RT) groups (n = 490 each). Patients in the RT group harbored significantly higher 3- and 5-year overall survival (OS) and cancer-specific survival (CSS) rates compared to those in the No RT group (both P < 0.05). Furthermore, RT was an independent favorable prognostic factor of OS as well as CSS in multivariate analysis, both before [OS: hazard ratio (HR) 0.840, 95% confidence interval (CI) 0.739-0.954, P = 0.007; CSS: HR 0.847, 95% CI 0.741-0.967, P = 0.014] and after (OS: HR 0.854, 95% CI 0.736-0.970, P = 0.016; CSS: HR 0.848, 95% CI 0.735-0.978, P = 0.023) PSM. In subgroup analysis, American Joint Committee on Cancer (AJCC) stage II and III, tumor size 5-10 cm, patients who underwent no surgery, or patients who received chemotherapy could significantly benefit from RT (all P < 0.05). To sum up, our findings suggested that RT could prolong the survival of patients with pulmonary LCNEC, especially those with stage II and III, tumor size 5-10 cm, those with no surgery, or those who received chemotherapy.