Prognostic relevance of clonal hematopoiesis in myeloid neoplastic transformation in patients with follicular lymphoma treated with radioimmunotherapy.

While novel radioisotope therapies continue to advance cancer care, reports of therapy-related myeloid neoplasms (t-MN) have generated concern. The prevalence and role of clonal hematopoiesis (CH) in this process remain to be defined. We hypothesized that: (i) CH is prevalent in relapsed follicular lymphoma and is associated with t-MN transformation, and (ii) radiation in the form of radioimmunotherapy (RIT) plays a role in clonal progression. In this retrospective cohort study, we evaluated the prevalence and prognostic impact of CH on clinical outcomes in 58 heavily pre-treated follicular lymphoma patients who received RIT. Patients had been given a median of four lines of therapy before RIT. The prevalence of CH prior to RIT was 46%, while it was 67% (P=0.15) during the course of RIT and subsequent therapies in the paired samples. Fourteen (24%) patients developed t-MN. Patients with t-MN had a higher variant allele fraction (38% vs. 15%; P=0.02) and clonal complexity (P=0.03) than those without. The spectrum of CH differed from that in age-related CH, with a high prevalence of DNA damage repair and response pathway mutations, absence of spliceosome mutations, and a paucity of signaling mutations. While there were no clear clinical associations between RIT and t-MN, or overall survival, patients with t-MN had a higher mutant clonal burden, along with extensive chromosomal abnormalities (median survival, afer t-MN diagnosis, 0.9 months). The baseline prevalence of CH was high, with an increase in prevalence on exposure to RIT and subsequent therapies. The high rates of t-MN with marked clonal complexities and extensive chromosomal damage underscore the importance of better identifying and studying genotoxic stressors accentuated by therapeutic modalities.

Pretherapeutic estimated glomerular filtration rate predicts development of chronic kidney disease in patients receiving PSMA-targeted radioligand therapy.

BACKGROUND: Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) may be associated with renal toxicity. We aimed to identify predictive parameters for the development of chronic kidney disease (CKD) in patients with metastatic castration resistant prostate cancer (mCRPC) undergoing RLT. METHODS: In 46 mCRPC patients scheduled for Lu-177-PSMA-RLT, pretherapeutic estimated glomerular filtration rate (eGFR [ml/min/1.73 m2 ]), Tc-99m-mercaptoacetyltriglycine (Tc-99m-MAG3) clearance and baseline Ga-68-PSMA-ligand positron emission tomography (PET)-derived renal cortical uptake and PSMA-tumor volume (TV) were determined. We tested the predictive capability of these parameters and clinical risk factors for the occurrence of CKD (defined as CTCAE vers. 5.0 grade 2 or higher) during follow-up. RESULTS: After 4 ± 3 cycles of RLT average eGFR declined from 76 ± 17 to 72 ± 20 ml/min/1.73 m2 (p = 0.003). Increased estimated renal radiation dose (eRRD) was significantly associated with renal functional decline (p = 0.008). During follow-up, 16/46 (30.4%) developed CKD grade 2 (no grade 3 or higher). In receiver operating characteristic (ROC) analysis, pretherapeutic eGFR was highly accurate in identifying the occurrence of CKD vs no CKD with an area under the curve (AUC) of 0.945 (p < 0.001; best threshold, 77 ml/min/1.73 m2 ), followed by Tc-99m-MAG3-derived tubular extraction rate (TER; AUC, 0.831, p < 0.001; best threshold, 200 ml/min/1.73 m2 ). Renal PET signal (p = 0.751) and PSMA-TV (p = 0.942), however, were not predictive. Kaplan-Meier analyses revealed adverse renal outcome for patients with lower eGFR (p = 0.001) and lower scintigraphy-derived TER (p = 0.009), with pretherapeutic eGFR emerging as the sole predictive parameter in multivariate analysis (p = 0.007). CONCLUSION: Serious adverse renal events are not a frequent phenomenon after PSMA-targeted RLT. However, in patients developing moderate CKD after RLT, pretherapeutic eGFR is an independent predictor for renal impairment during follow-up.

90-yttrium-ibritumomab tiuxetan as first-line treatment for follicular lymphoma: updated efficacy and safety results at an extended median follow-up of 9.6 years.

Radioimmunotherapy with 90-yttrium-ibritumomab tiuxetan (90Y-IT) as first-line treatment in patients with follicular lymphoma (FL) demonstrated promising results with a complete remission (CR) rate of 56% and a median progression-free survival (PFS) of 26 months, when initially analyzed after a median follow-up of 30.6 months. The aim of this long-term follow-up was to investigate whether clinical benefits were maintained and new safety signals appeared. Fifty-nine patients, aged ≥ 50 years, with FL grade 1 to 3A in stages II to IV were treated with 90Y-IT as first-line therapy. If CR without evidence of minimal residual disease (MRD), partial response or stable disease was achieved 6 months after treatment, patients were observed without further treatment. Patients with CR but persisting MRD received consolidation therapy with rituximab. The primary endpoint was the clinical response rate. Secondary endpoints were time to progression, safety, and tolerability. After a median follow-up of 9.6 years, median PFS was 3.6 years, and 8-year PFS was 38.3%. Median overall survival (OS) was not reached during the extended follow-up, and 8-year OS amounted to 69.2%. Age 65 years and above or disease progression within 24 months of treatment were significantly associated with shorter OS. An important finding was the lack of new safety signals. In particular, no increase in secondary malignancies or transformation into aggressive lymphoma was observed compared to trials with a similar follow-up. In summary, 90Y-IT as first-line treatment demonstrates a favorable safety profile and long-term clinical activity in a substantial fraction of FL patients in need of therapy. ClinicalTrials.gov Identifier: NCT00772655.

An autoimmune-based, paraneoplastic neurologic syndrome following checkpoint inhibition and concurrent radiotherapy for merkel cell carcinoma: case report.

PURPOSE: Merkel cell carcinoma is highly sensitive to both radiation and immunotherapy. Moreover, concurrent radioimmunotherapy may capitalize on anti-tumor immune activity and improve Merkel cell treatment response, although an enhanced immune system may cross-react with native tissues and lead to significant sequelae. METHODS: Here we present a case study of a patient with metastatic Merkel cell carcinoma treated with radiotherapy concurrent with pembrolizumab. RESULTS: After radioimmunotherapy, the patient developed sensory neuropathy, visual hallucinations, and mixed motor neuron findings. Neurologic dysfunction progressed to profound gastrointestinal dysmotility necessitating parenteral nutrition and intubation with eventual expiration. CONCLUSION: This case represents a unique autoimmune paraneoplastic neurologic syndrome, likely specific to neuroendocrine tumors and motivated by concurrent radioimmunotherapy. Recognition of the potential role of radioimmunotherapy may provide an advantage in anticipating these severe sequelae.

Safety Evaluation of an Alpha-Emitter Bismuth-213 Labeled Antibody to (1→3)-ß-Glucan in Healthy Dogs as a Prelude for a Trial in Companion Dogs with Invasive Fungal Infections.

Background: With the limited options available for therapy to treat invasive fungal infections (IFI), radioimmunotherapy (RIT) can potentially offer an effective alternative treatment. Microorganism-specific monoclonal antibodies have shown promising results in the experimental treatment of fungal, bacterial, and viral infections, including our recent and encouraging results from treating mice infected with Blastomyces dermatitidis with 213Bi-labeled antibody 400-2 to (1→3)-ß-glucan. In this work, we performed a safety study of 213Bi-400-2 antibody in healthy dogs as a prelude for a clinical trial in companion dogs with acquired invasive fungal infections and later on in human patients with IFI. Methods: Three female beagle dogs (≈6.1 kg body weight) were treated intravenously with 155.3, 142.5, or 133.2 MBq of 213Bi-400-2 given as three subfractions over an 8 h period. RBC, WBC, platelet, and blood serum biochemistry parameters were measured periodically for 6 months post injection. Results: No significant acute or long-term side effects were observed after RIT injections; only a few parameters were mildly and transiently outside reference change value limits, and a transient atypical morphology was observed in the circulating lymphocyte population of two dogs. Conclusions: These results demonstrate the safety of systemic 213Bi-400-2 administration in dogs and provide encouragement to pursue evaluation of RIT of IFI in companion dogs.

Advances in targeted alpha therapy for prostate cancer.

Amongst therapeutic radiopharmaceuticals, targeted alpha therapy (TαT) can deliver potent and local radiation selectively to cancer cells as well as the tumor microenvironment and thereby control cancer while minimizing toxicity. In this review, we discuss the history, progress, and future potential of TαT in the treatment of prostate cancer, including dosimetry-individualized treatment planning, combinations with small-molecule therapies, and conjugation to molecules directed against antigens expressed by prostate cancer cells, such as prostate-specific membrane antigen (PSMA) or components of the tumor microenvironment. A clinical proof of concept that TαT is efficacious in treating bone-metastatic castration-resistant prostate cancer has been demonstrated by radium-223 via improved overall survival and long-term safety/tolerability in the phase III ALSYMPCA trial. Dosimetry calculation and pharmacokinetic measurements of TαT provide the potential for optimization and individualized treatment planning for a precision medicine-based cancer management paradigm. The ability to combine TαTs with other agents, including chemotherapy, androgen receptor-targeting agents, DNA repair inhibitors, and immuno-oncology agents, is under investigation. Currently, TαTs that specifically target prostate cancer cells expressing PSMA represents a promising therapeutic approach. Both PSMA-targeted actinium-225 and thorium-227 conjugates are under investigation. The described clinical benefit, safety and tolerability of radium-223 and the recent progress in TαT trial development suggest that TαT occupies an important new role in prostate cancer treatment. Ongoing studies with newer dosimetry methods, PSMA targeting, and novel approaches to combination therapies should expand the utility of TαT in prostate cancer treatment.

Bevacizumab Radioimmunotherapy (RIT) with Accelerated Blood Clearance Using the Avidin Chase.

The overexpression of vascular endothelial growth factor (VEGF) in varying types of solid tumor renders radioimmunotherapy (RIT) with the anti-VEGF antibody bevacizumab (BV) a promising treatment. However, the slow blood clearance of BV, which may increase the occurrence risk of hematotoxicity, hinders the application of BV-RIT. Using the avidin chase is a long-known blood clearance enhancement strategy for biotinylated-mAb. To enhance RIT efficacy by increasing the radioactivity dose, we evaluated the ability of avidin to accelerate the blood clearance of yttrium-90 (90Y)-labeled biotinylated BV (90Y-Bt-BV) in a xenograft mouse model of triple-negative breast cancer (TNBC). The biodistribution study in the TNBC xenograft mice confirmed the high and specific tumor accumulation of the indium-111 (111In)-BV. The blood clearance enhancement effect of the avidin chase was demonstrated in the normal mouse studies with 111In-Bt-BV. In the subsequent biodistribution studies with the tumor-bearing mice, an optimized dose of avidin injection subsequent to 111In-Bt-BV with an appropriate biotin valency successfully accelerated the blood clearance of 111In-Bt-BV without impairing its tumor accumulation level. The avidin chase enabled an increase in the maximum tolerated dose of 90Y-Bt-BV to twice as much as that of 90Y-BV in tumor-bearing mice and thereby significantly improved the therapeutic effect of 90Y-Bt-BV compared to 90Y-BV ( p < 0.05). These results underscored the potential usefulness of 90Y-bevacizumab-RIT with the avidin chase for the treatment of VEGF-positive tumors.

Bevacizumab-associated Bowel Microperforation in a Patient With Neuroblastoma.

The antivascular endothelial growth factor antibody, bevacizumab, is effective against several malignancies in adults but unproven in pediatric oncology. In early phase pediatric studies toxicities were similar to those in adults. Bowel perforation in adults is a rare but serious toxicity, but has not been hitherto reported in children. A 5-year-old boy with chemoresistant neuroblastoma treated with bevacizumab plus radioimmunotherapy developed acute abdominal pain. Computed tomography scan showed free abdominal air and pneumatosis coli. Emergency laparotomy and bowel diversion were performed leading to complete recovery and timely continuation of antineuroblastoma therapy. Early recognition and rapid intervention can prevent a catastrophic outcome in bevacizumab-related bowel perforation.

Repeated adjuvant anti-CEA radioimmunotherapy after resection of colorectal liver metastases: Safety, feasibility, and long-term efficacy results of a prospective phase 2 study.

BACKGROUND: In previous work, a single administration of anticarcinoembryonic antigen (anti-CEA) 131 I-labetuzumab radioimmunotherapy (RIT) after complete resection of colorectal liver metastases was well tolerated and significantly improved survival compared with controls. In the current phase 2 trial, the authors studied repeated RIT in the same setting, examining safety, feasibility, and efficacy. METHODS: Sixty-three patients (median age, 64.5 years) received RIT at 40 to 50 millicuries/m2 per dose. Before the receipt of RIT, restaging was performed with computed tomography/magnetic resonance imaging and 18 F-fluorodeoxyglucose-positron emission to confirm that patients were "truly adjuvant." Patients who had elevated serum CEA levels or radiographically inconclusive new lesions were classified as "possibly nonadjuvant," but they also received RIT. Time to progression (TTP), overall survival (OS), and cause-specific survival (CSS) were calculated. The median follow-up was 54 months. RESULTS: After the first course of RIT, 14 of 63 patients experienced National Cancer Institute Common Toxicity Criteria grade 4 hematotoxicity; 19 patients did not receive the second course of RIT because of impaired performance status (N = 5) or relapse (N = 14). After the second course of RIT, 9 of 44 patients experienced National Cancer Institute Common Toxicity Criteria grade 4 hematotoxicity. Five patients developed myelodysplastic syndrome (MDS) from 22 to 55 months after their last RIT. The median TTP, OS, and CSS for all patients were 16, 55, and 60 months, respectively. The "truly adjuvant" patients (N = 39) had an improved median TTP (not reached vs 6.1 months; hazard ratio, 0.12; P < .001), OS (75.6 vs 33.4 months; hazard ratio, 0.44; P = .014), and CSS (not reached vs 41.4 months; hazard ratio,0.42; P = .014) compared with "possibly nonadjuvant" patients (N = 24). CONCLUSIONS: Repeated RIT with 131 I-labetuzumab is feasible but is associated with hematotoxicity. Survival is very encouraging, especially for "truly adjuvant" patients. However, the maximum safe dose of 131 I-labetuzumab is a single administration of 50 millicuries/m2 . Cancer 2017;123:638-649. © 2016 American Cancer Society.

Risk of histological transformation and therapy-related myelodysplasia/acute myeloid leukaemia in patients receiving radioimmunotherapy for follicular lymphoma.

Histological transformation (HT) of follicular lymphoma (FL) to an aggressive lymphoma after chemotherapy remains a key issue. The incidence of HT after radioimmunotherapy (RIT) is unknown. This single institution study analysed the risk of HT in FL after treatment with yttrium-90 ibritumomab tiuxetan in 115 consecutive patients treated during 1987-2012. RIT was administered for progressive FL in 111 (97%) patients and as first-line therapy in the remaining 4. 28% (n = 32) had HT, occurring at a median of 60 months from diagnosis and 20 months after RIT. 48% (12/25) of patients who received fludarabine developed HT. The estimated 10-year risk of HT in the fludarabine and non-fludarabine groups was 67% and 26% respectively (P = 0·015). Only prior fludarabine was significantly associated with predicting the risk of HT after RIT. 8% (9/115) of patients developed therapy-related myelodysplastic syndrome/acute myeloid leukaemia (tMDS/AML) at a median of 41·4 months (range, 5-89). The estimated 10-year risk of tMDS/AML in non-fludarabine treated patients (n = 90) versus fludarabine treated (n = 25) was 13% and 29%, respectively. The estimated overall risk of FL undergoing HT at 10 years without fludarabine exposure appears similar to patients reported in the literature that have not received RIT. Patients with prior purine-analogue therapy are at significantly higher risk of HT.

Lymphoma: current status of clinical and preclinical imaging with radiolabeled antibodies.

Lymphoma is a complex disease that arises from cells of the immune system with an intricate pathology. While lymphoma may be classified as Hodgkin or non-Hodgkin, each type of tumor is genetically and phenotypically different and highly invasive tissue biopsies are the only method to investigate these differences. Noninvasive imaging strategies, such as immunoPET, can provide a vital insight into disease staging, monitoring treatment response in patients, and dose planning in radioimmunotherapy. ImmunoPET imaging with radiolabeled antibody-based tracers may also assist physicians in optimizing treatment strategies and enhancing patient stratification. Currently, there are two common biomarkers for molecular imaging of lymphoma, CD20 and CD30, both of which have been considered for investigation in preclinical imaging studies. In this review, we examine the current status of both preclinical and clinical imaging of lymphoma using radiolabeled antibodies. Additionally, we briefly investigate the role of radiolabeled antibodies in lymphoma therapy. As radiolabeled antibodies play critical roles in both imaging and therapy of lymphoma, the development of novel antibodies and the discovery of new biomarkers may greatly affect lymphoma imaging and therapy in the future.

Optimizing Radiotherapy with Immunotherapeutic Approaches.

Several factors must be considered to successfully integrate immunotherapy with radiation into clinical practice. One such factor is that concepts arising from preclinical work must be tested in combination with radiation in preclinical models to better understand how combination therapy will work in patients; examples include checkpoint inhibitors, tumor growth factor-beta (TGF-ß) inhibitors, and natural killer (NK) cell therapy. Also, many radiation fields and fractionation schedules typically used in radiation therapy had been standardized before the introduction of advanced techniques for radiation planning and delivery that account for changes in tumor size, location, and motion during treatment, as well as uncertainties introduced by variations in patient setup between treatment fractions. As a result, radiation therapy may involve the use of large treatment volumes, often encompassing nodal regions that may not be irradiated with more conformal techniques. Traditional forms of radiation in particular pose challenges for combination trials with immunotherapy. This chapter explores these issues in more detail and provides insights as to how radiation therapy can be optimized to combine with immunotherapy.

A phase 2 study of inotuzumab ozogamicin in patients with indolent B-cell non-Hodgkin lymphoma refractory to rituximab alone, rituximab and chemotherapy, or radioimmunotherapy.

This phase 2 study evaluated the efficacy and safety of inotuzumab ozogamicin (InO) in patients with indolent B-cell non-Hodgkin lymphoma (NHL) refractory to rituximab alone, rituximab plus chemotherapy or anti-CD20 radioimmunotherapy. Patients received InO 1·8 mg/m(2) intravenously on a 28-d cycle for a planned 4-8 cycles. The initial InO dose and schedule could be adjusted for tolerability and patients were allowed to receive 2 additional cycles (up to 8 total) after achieving a complete response (CR). The primary endpoint was overall response. Eighty-one patients were enrolled, among whom 48 (59%) received ≥3 InO cycles and 13 (16%) completed the treatment phase. The overall response rate was 67% (CR, 31%). Median (95% confidence interval) progression-free survival was 12·7 (8·9-26·9) months; median overall survival was not reached. Haematological adverse events (AEs) were common, particularly thrombocytopenia (74%) and neutropenia (56%). These were also the most common AEs leading to treatment discontinuation (37% and 11%, respectively); 58% of patients reported AEs leading to treatment discontinuation. InO demonstrated robust activity in these heavily pretreated patients, although treatment duration was limited by haematological toxicities. Additional studies may determine dosing regimens that allow for reduced toxicity.

Short duration immunochemotherapy followed by radioimmunotherapy consolidation is effective and well tolerated in relapsed follicular lymphoma: 5-year results from a UK National Cancer Research Institute Lymphoma Group study.

UNLABELLED: We report a phase II study to evaluate the efficacy and toxicity of abbreviated immunochemotherapy followed by (90) Y Ibritumomab tiuxetan ((90) Y-IT) in patients with recurrent follicular lymphoma. Of the 52 patients enrolled, 50 were treated with three cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone) or R-CVP (rituximab, cyclophosphamide, vincristine, prednisolone), followed by (90) Y-IT regimen (15 MBq/kg, maximum 1200 MBq) preceded by two infusions of 250 mg/m(2) rituximab. The overall response rate was 98% with complete response (CR) 30% and partial response (PR) 68%. 18 patients with a PR following chemotherapy improved to a CR following (90) Y-IT: a conversion rate of 40%. Seven patients with PR following (90) Y-IT subsequently improved to a CR 12-18 months later, leading to an overall CR rate of 44%. With a median follow-up of 5 years, median progression-free survival was 23·1 months and overall survival was 77·5% at 5 years. High trough serum rituximab levels (median 112 µg/ml; range 52-241) were attained after four doses of rituximab, prior to (90) Y-IT; this was not found to influence response rates. The treatment was well tolerated with few (13·5%) grade 3 or 4 infective episodes and manageable haematological toxicity. Abbreviated immunochemotherapy followed by (90) Y-IT is an effective and well-tolerated treatment in recurrent follicular lymphoma patients previously exposed to rituximab. TRIAL REGISTRATION: clinicaltrials.gov identifier: NCT00637832.

Long-term complication in follicular lymphoma: assessing the risk of secondary neoplasm in 242 patients treated or not with 90-yttrium-ibritumomab-tiuxetan.

BACKGROUND: Non-Hodgkin lymphoma patients have a 25% increased risk of secondary primary neoplasms (SPNs). Regarding the controversy about the increased risk of SPN in patients exposed to radioimmunotherapy (RIT), we have analyzed this issue in a cohort of follicular lymphoma (FL) patients treated with/without RIT. PATIENTS AND METHODS: A retrospective study including all consecutive FL patients diagnosed since 2001 was performed. Demographic, clinical data including the incidence of any kind of neoplasm (excluding basocellular skin carcinoma) were recorded. RESULTS: A total of 242 patients were registered, male/female: 103/139, mean age: 59.9 yr (15-86), stage IV (57.8%), and Follicular Lymphoma Prognostic Index (FLIPI) low-risk (62.15%) predominance. Ninety-six patients (39.7%) were treated with 90Y-IT. The median follow-up for patients treated or not with 90Y-IT was 61 (8-273) and 38 (1-171) months. With respect to SPN incidence, 38 (15.6%) patients have at least two cancers, in 17 (44.7%), FL was the SPN; for the rest (226), the global incidence of SPNs was 9.3% (21), but there were no differences related to the exposition or not to 90Y-IT (P = 0.26). In seven patients, more than two (2-6) different therapies were registered; four were exposed to fludarabine-based therapy, three to radiotherapy and two to autologous stem-cell transplantation, and in the RIT cohort, two patients developed myelodysplastic syndrome. CONCLUSION: This is one of the largest single institution reports assessing the risk of SPN in FL patients treated (96) or not (146) with 90Y-IT. It seems that 90Y-IT does not increase significantly the risk of SPN but avoiding its use after fludarabine and other intense cytotoxic schemes is recommended.

Effectiveness and Safety of Radioactive Iodine Therapy in Childhood Graves' Disease in Khon Kaen, Thailand.

Background: Graves' disease (GD) is the most common cause of hyperthyroidism in children and adolescents. Treatments consist of medication, radioactive iodine (RAI) therapy and surgery. Currently, radioactive iodine therapy is the first line treatment in many medical centers. Objective: To evaluate the effectiveness and safety of RAI therapy in childhood GD. Material and Method: A retrospective study was performed in 46 GD patients, aged at onset <15 years, who had undergone RAI therapy at the age >10 years. Goiter grading, evidence of hypothyroidism, severity of ophthalmopathy, RAI dosage and side effects of RAI therapy were evaluated. Results: The cure rate was 95.6%. All participating patients had goiter reduction (p = 0.005). Hypothyroidism was induced in 33 (71.7%) and 11 (23.9%) patients after the first and second RAI therapy. The total RAI dosage was significantly higher in the patients with failure response (p = 0.001). The average time to induce hypothyroidism after the first RAI therapy was 127.5 (IQR: 94.5-223.0) days. All of the patients had improvement of ophthalmopathy and none had thyroid carcinoma during the follow-up period of 42.5 (IQR: 17-52) months. Conclusion: Radioactive iodine therapy is effective and safe in the treatment of children and adolescents with Graves' disease.

A randomized study comparing the effectiveness of microwave ablation radioimmunotherapy and postoperative adjuvant chemoradiation in the treatment of non-small cell lung cancer.

PURPOSE: To evaluate the differences in the outcomes of patients with stage II and IIIa non-small cell lung cancer (NSCLC) treated with either 131I-labeled mouse/human chimeric monoclonal antibody against intracellular DNA exposed in necrotic and degenerating regions of tumors (131I-chTNT-mediated radioimmunotherapy) combined with percutaneous microwave coagulation therapy (PMCT) guided by computed tomography (CT) or with postoperative adjuvant chemoradiation. METHODS: Ninety-six patients with stage II and IIIa NSCLC were randomized into two groups. Group A included 49 patients who were treated with chemotherapy with docetaxel and cisplatin and three-dimensional conformal radiotherapy 3-4 weeks after surgery. Group B included 47 patients treated with 131I-chTNT and PMCT sequentially, with follow-up chemotherapy. RESULTS: The survival rates of patients in group A for the first and second years were 79.59% and 48.98%, respectively. The median survival was 23.0 months. Survival rates at 1 and 2 years for group B were 82.98% and 53.19%, respectively and the median survival was 29.1 months. The survival rate of group B patients for the first and second years was better compared with group A, and the difference in median survival between the groups was statistically significant (p<0.05). However, median survival and the incidence of adverse events were not significantly different between the two groups. CONCLUSIONS: 131I-chTNT radioimmunotherapy with PMCT has a complementary effect in NSCLC, which can effectively improve therapeutic ratio and survival of patients effectively and has the same effect as that of post-operative adjuvant chemoradiation.

Radioimmunotherapy--a potential novel tool for pancreatic cancer therapy?

Pancreatic cancer is one of the most severe cancers and is predicted to rise up to the number two cancer killer by 2030. The ineffective treatment options available and that the cancer is silent until very late in its course are the main reasons for the poor outcome of the disease. Surgery is the only curative option but only available for 10-15 % of the patients, but even then many relapse due to metastases. Many new treatments are under way, and one of the promising ones is radioimmunotherapy (RIT). This review includes clinical trials with RIT in pancreatic cancer as well as a review of adverse events observed during treatment of other solid tumors. Additionally, preclinical studies are reviewed with emphasis on effect, adverse events, the tumor targeting as well as isotope function. Four clinical trials with pancreatic cancer have been conducted with positive results, and one phase III trial is underway. The use of RIT in patients with solid tumors has proven to be well tolerated, and the adverse effects are almost exclusively hematological. Multiple targets and isotopes have been evaluated preclinically, alone, or in combination with existing drug options. Smaller tumors have in several studies completely regressed, while larger ones have stabilized or progressed more slowly. Pancreatic cancer is one of the solid tumors where RIT have reached the longest. The tumor heterogeneity will most likely leave room for more than one treatment option, and several aspiring therapies are under way. RIT may become part of multimodality tumor-directed therapy for pancreatic cancer.

Advancing radioimmunotherapy and its future role in non-Hodgkin lymphoma.

Radioimmunotherapy is an effective treatment modality with an acceptable toxicity profile in both indolent B-cell non-Hodgkin lymphoma and histologic transformation. Its ease of administration from a patient's perspective sets it apart from chemoimmunotherapy regimens. It has demonstrated efficacy in a range of different treatment scenarios. Despite its promise as a treatment modality, radioimmunotherapy has been seldom used, and one of the previously available agents is now off the market. Radioimmunotherapy has shown impressive activity in both the relapsed and upfront settings in follicular lymphoma, histologic transformation, as consolidation after chemotherapy, and in conjunction with high-dose chemotherapy and autologous stem cell support. Future efforts should focus on its optimal employment in the upfront setting for follicular lymphoma as well as further investigation of the promising activity in histologic transformation.

Safety and efficacy of (90) yttrium-ibritumomab-tiuxetan for untreated follicular lymphoma patients. An Italian cooperative study.

(90) Yttrium ((90) Y)-Ibritumomab-Tiuxetan combines the targeting advantage of a monoclonal antibody with the radiosensitivity of Follicular Lymphoma (FL). Previous studies showed that 90Y-IT is safe and effective in relapsed/refractory indolent FL, irrespective of prior treatment with rituximab. This multicentre trial aimed to evaluate the safety and the efficacy of "upfront" single-agent ((90) Y)-Ibritumomab-Tiuxetan in advanced-stage FL. The primary objective was the incidence of responses in terms of complete (CR) and partial remission (PR). Fifty patients with stage II "bulky", III or IV FL received a single treatment course with ((90) Y)-Ibritumomab-Tiuxetan as initial therapy. The median age was 60 years. Bone marrow involvement (<25%) was observed in 24 patients (48%) and 7 (14%) had an elevated lactate dehydrogenase level. The overall response (ORR) and CR rates were 94% and 86%, respectively with a median follow-up of 38·8 months. The median progression-free survival (PFS) was not reached, whereas the 3-year estimated PFS and overall survival (OS) rate was 63·4% and 90%, respectively. Grade 3/4 neutropenia and thrombocytopenia occurred in 30% and 26% of patients respectively; none experienced grade 3/4 non-haematological toxicity. No cases of secondary haematological malignancies were observed. ((90) Y)-Ibritumomab-Tiuxetan was demonstrated to be highly effective and safe as first-line treatment for advanced-stage FL.