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BACKGROUND: Combinations of vascular endothelial growth factor receptor (VEGFR) tyrosine kinase inhibitors (TKIs) plus immune checkpoint inhibitor (ICI) against PD1/PD-L1 are the standard first-line therapy for patients with metastatic renal cell carcinoma (mRCC), irrespective of the prognostic class. OBJECTIVE: To investigate the feasibility and safety of withdrawing VEGFR-TKI but continuing anti-PD1/PD-L1 in patients who achieve a response to their combination. DESIGN, SETTING, AND PARTICIPANTS: This was a single-arm phase 2 trial in patients with treatment-naïve mRCC with prior nephrectomy, without symptomatic/bulky disease and no liver metastases. INTERVENTION: Enrolled patients received axitinib + avelumab; after 36 wk of therapy those who achieved a tumour response interrupted axitinib and continued avelumab maintenance until disease progression. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary endpoint was the rate of patients without progression 8 wk after the axitinib interruption. The secondary endpoints were the median value for progression-free (mPFS) and overall (mOS) survival and the safety in the overall population. RESULTS AND LIMITATIONS: Seventy-nine patients were enrolled and 75 were evaluated for efficacy. A total of 29 (38%) patients had axitinib withdrawn, as per the study design, with 72% of them having no progression after 8 wk and thus achieving the primary endpoint. The mPFS of the overall population was 24 mo, while the mOS was not reached. The objective response rate was 76% (12% complete response and 64% partial response), with 19% of patients having stable disease. In the patients who discontinued axitinib, the incidence of adverse events of any grade was 59% for grade 3 and 3% for grade 4. This study was limited by the lack of a comparative arm. CONCLUSIONS: The TIDE-A study demonstrates that the withdrawal of VEGFR-TKI with ICI maintenance is feasible for selected mRCC patients with evidence of a response to the VEGFR-TKI + ICI combination employed in first-line therapy. Axitinib interruption with avelumab maintenance leads to decreased side effects and should be investigated further as a new strategy to delay tumour progression. PATIENT SUMMARY: We evaluated whether certain patients with advanced kidney cancer treated with the fist-line combination of axitinib plus avelumab can interrupt the axitinib in case of a tumour response after 36 wk of therapy. We found that axitinib interruption improved the safety of the combination, while the maintenance with avelumab might delay tumour progression.
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Several concerns have been raised about a causal relationship between COVID-19 mRNA-based vaccines and the development of herpes zoster (HZ). We performed a prospective analysis of the Vax-On-Third-Profile study to investigate the incidence of HZ after the third dose of mRNA-BNT162b2 (tozinameran) and its correlation with immune responses. Patients who had received a booster dose and had been actively treated for at least 8 weeks were eligible. Serologic assessment was performed before the third dose of tozinameran (timepoint-1) and 4 weeks later (timepoint-2). We also assessed the incidence of SARS-CoV-2 breakthrough infections at predefined time points. The current analysis included 310 patients, of whom 109 (35.2%) and 111 (35.8%) were being treated with targeted therapies and cytotoxic chemotherapy, respectively. All participants received a third dose of tozinameran between September 26 and October 30, 2021. After a mean follow-up of 17.3 (IQR 15.1-18.4) months, HZ occurred in 8 recipients, for a cumulative incidence of 2.6%, and an incidence rate of 0.310 per person-year (95% CI 0.267-0.333). All HZ cases occurred within 30 days of booster dosing (range 5-29 days), with a median time to onset of 15 (IQR 9-22) days. Among the 7 patients (2.2%) who also contracted a SARS-CoV-2 infection, all cases preceded COVID-19 outbreaks. No instances of complicated HZ were reported. In multivariate analysis, impaired T helper and T cytotoxic cell counts independently correlated with HZ occurrence. These findings provide the first evidence that cancer patients on active treatment have a not negligible risk of developing HZ within 30 days after the third dose of tozinameran. The favorable clinical outcome of all observed cases confirms that protective effects of boosters in reducing the risk of severe COVID-19 outweigh the potential risk of HZ occurrence.
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COVID-19 , Herpes Zóster , Neoplasias , Humanos , Vacuna BNT162 , Estudios Prospectivos , SARS-CoV-2 , COVID-19/prevención & control , Herpes Zóster/prevención & control , ARN MensajeroRESUMEN
BACKGROUND: The clinical implications of the third dose of coronavirus disease 2019 (COVID-19) vaccines in patients receiving immune checkpoint inhibitors are currently unknown. We performed a prospective analysis of the Vax-On-Third study to investigate the effects of antibody response on immune-related adverse events (irAEs) and disease outcomes. METHODS: Recipients of the booster dose of SARS-CoV-2 mRNA-BNT162b2 vaccine who had received at least one course of an anti-PD-1/PD-L1 treatment before vaccination for an advanced solid malignancy were eligible. RESULTS: The current analysis included 56 patients with metastatic disease (median age: 66 years; male: 71%), most of whom had a lung cancer diagnosis and were being treated with pembrolizumab- or nivolumab-based regimens. The optimal cut-point antibody titer of 486 BAU/mL allowed a dichotomization of recipients into low-responders (Low-R, < 486 BAU/mL) or high-responders (High-R, ≥ 486 BAU/mL). After a median follow-up time of 226 days, 21.4% of patients experienced moderate to severe irAEs without any recrudescence of immune toxicities preceding the booster dose. The frequencies of irAE before and after the third dose did not differ, but an increase in the cumulative incidence of immuno-related thyroiditis was observed within the High-R subgroup. On multivariate analysis, an enhanced humoral response correlated with a better outcome in terms of durable clinical benefit, which resulted in a significant reduction in the risk of disease control loss but not mortality. CONCLUSIONS: Our findings would strengthen the recommendation not to change anti-PD-1/PD-L1 treatment plans based on current or future immunization schedules, implying that all these patients should be closely monitored.
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Vacuna BNT162 , COVID-19 , Humanos , Masculino , Anciano , Inhibidores de Puntos de Control Inmunológico , Antígeno B7-H1 , SARS-CoV-2 , COVID-19/prevención & control , Recurrencia Local de Neoplasia , ARN MensajeroRESUMEN
BACKGROUND: Anti-SARS-CoV-2 mRNA vaccines can deeply affect cell-mediated immune responses in immunocompromised recipients, including cancer patients receiving active treatments. The clinical implications of changes in peripheral blood lymphocyte subsets following the third dose of mRNA-BNT162b2 vaccination (tozinameran) in patients on immune checkpoint blockade are not fully understood. We conducted a prospective analysis of the Vax-On-Third-Profile study to evaluate the impact of circulating lymphocyte dynamics on disease outcomes in this subgroup of patients. METHODS: Recipients of booster dosing who had received before vaccination at least one course of an anti-PD-1/PD-L1 treatment for an advanced solid tumor were eligible. Immunophenotyping of peripheral blood was performed before the third dose of tozinameran (timepoint-1) and four weeks later (timepoint-2) to quantify the absolute counts of lymphocyte subpopulations, including CD3+CD4+ T cells, CD3+CD8+ T cells, B cells, and NK cells. Logistic regression was used to analyze the relationship between lymphocyte subsets and durable clinical benefit (DCB). The log-rank test and Cox regression model were applied to evaluate the relationship between lymphocyte subpopulations and both vaccine-related time-to-treatment failure (V-TTF) and overall survival (OS). RESULTS: We included a total of 56 patients with metastatic disease who were given a third dose of tozinameran between 23 September and 7 October 2021 (median age: 66 years; male: 71%). Most recipients had a diagnosis of lung cancer and were being treated with pembrolizumab or nivolumab. Compared to baseline, the third immunization resulted in an incremental change in the median counts of all lymphocyte subpopulations, which was statistically significant only for NK cells (p < 0.001). A significant correlation was found between NK cell counts and DCB at timepoint-2 (p < 0.001). Multivariate logistic regression analysis of DCB confirmed the predictive significance of high-level NK cell counts (p = 0.020). In multivariate Cox regression analysis, high-level NK cell counts independently predicted longer V-TTF [HR 0.34 (95% CI 0.14-0.80), p = 0.014] and OS [HR 0.36 (95% CI 0.15-0.89), p = 0.027]. CONCLUSIONS: Our data suggest expansion of NK cell counts as the most noteworthy change in circulating lymphocytes after the third dose of tozinameran in cancer patients receiving PD-1/PD-L1-targeted agents. This change correlated with enhanced therapeutic efficacy, improving the rate of disease control, and prolonging survival outcomes. Similar findings have not been previously reported, implying that they have proof-of-concept value and warrant further confirmation.
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(1) Background: The clinical implications of COVID-19 outbreaks following SARS-CoV-2 vaccination in immunocompromised recipients are a worldwide concern. Cancer patients on active treatment remain at an increased risk of developing breakthrough infections because of waning immunity and the emergence of SARS-CoV-2 variants. There is a paucity of data on the effects of COVID-19 outbreaks on long-term survival outcomes in this population. (2) Methods: We enrolled 230 cancer patients who were on active treatment for advanced disease and had received booster dosing of an mRNA-BNT162b2 vaccine as part of the Vax-On-Third trial between September 2021 and October 2021. Four weeks after the third immunization, IgG antibodies against the spike receptor domain of SARS-CoV-2 were tested in all patients. We prospectively evaluated the incidence of breakthrough infections and disease outcomes. The coprimary endpoints were the effects of antibody titers on the development of breakthrough infections and the impact of COVID-19 outbreaks on cancer treatment failure. (3) Results: At a median follow-up of 16.3 months (95% CI 14.5-17.0), 85 (37%) patients developed SARS-CoV-2 infection. Hospitalization was required in 11 patients (12.9%) and only 2 (2.3%) deaths related to COVID-19 outbreaks were observed. Median antibody titers were significantly lower in breakthrough cases than in non-cases (291 BAU/mL (95% CI 210-505) vs. 2798 BAU/mL (95% CI 2323-3613), p < 0.001). A serological titer cut-off below 803 BAU/mL was predictive of breakthrough infection. In multivariate testing, antibody titers and cytotoxic chemotherapy were independently associated with an increased risk of outbreaks. Time-to-treatment failure after booster dosing was significantly shorter in patients who contracted SARS-CoV-2 infection (3.1 months (95% CI 2.3-3.6) vs. 16.2 months (95% CI 14.3-17.0), p < 0.001) and had an antibody level below the cut-off (3.6 months (95% CI 3.0-4.5) vs. 14.6 months (95% CI 11.9-16.3), p < 0.001). A multivariate Cox regression model confirmed that both covariates independently had a worsening effect on time-to-treatment failure. (4) Conclusions: These data support the role of vaccine boosters in preventing the incidence and severity of COVID-19 outbreaks. Enhanced humoral immunity after the third vaccination significantly correlates with protection against breakthrough infections. Strategies aimed at restraining SARS-CoV-2 transmission in advanced cancer patients undergoing active treatment should be prioritized to mitigate the impact on disease outcomes.
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COVID-19 , Neoplasias , Humanos , Vacunas contra la COVID-19/uso terapéutico , Formación de Anticuerpos , SARS-CoV-2 , Vacuna BNT162 , Infección Irruptiva , Neoplasias/tratamiento farmacológicoRESUMEN
The aim of this study was to evaluate the association of circulating lymphocytes profiling with antibody response in cancer patients receiving the third dose of COVID-19 mRNA-BNT162b2 vaccine. Immunophenotyping of peripheral blood was used to determine absolute counts of lymphocyte subsets, alongside detection of IgG antibodies against receptor-binding-domain (RBD) of the SARS-CoV-2 Spike protein (S1) before booster dosing (timepoint-1) and four weeks afterward (timepoint-2). An IgG titer ≥ 50 AU/mL defined a positive seroconversion response. An IgG titer ≥ 4446 AU/mL was assumed as a correlate of 50% vaccine efficacy against symptomatic infections. A total of 258 patients on active treatment within the previous six months were enrolled between September 23 and October 7, 2021. The third dose resulted in an exponential increase in median anti-RBD-S1 IgG titer (P < 0.001), seroconversion rates (P < 0.001), and 50% vaccine efficacy rates (P < 0.001). According to ROC curve analysis, T helper and B cells were significantly associated with seroconversion responses at timepoint-1, whereas only B cells were relevant to 50% vaccine efficacy rates at timepoint-2. A positive linear correlation was shown between anti-RBD-S1 IgG titers and these lymphocyte subset counts. Multivariate analysis ruled out a potential role of T helper cells but confirmed a significant interaction between higher B cell levels and improved antibody response. These findings suggest that peripheral counts of B cells correlate with humoral response to the third dose of mRNA-BNT162b2 vaccine in actively treated cancer patients and could provide insights into a more comprehensive assessment of vaccination efficacy.
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Formación de Anticuerpos , Vacuna BNT162 , COVID-19 , Neoplasias , Humanos , Anticuerpos Antivirales/sangre , Vacuna BNT162/inmunología , COVID-19/prevención & control , Inmunoglobulina G/sangre , Linfocitos , Neoplasias/inmunología , SARS-CoV-2RESUMEN
Background Numerous research studies have looked into how the primary tumor location (PTL) affects patients' prognosis for colorectal cancer (CRC). Our research aimed to investigate the prognostic effects of PTL in patients with synchronous (SM) and metachronous (MM) colorectal cancer liver metastases (CRCLM). Material and methods From 2016 to 2021, we looked back at the records of patients at our institute who were affected by CRCLM. Results 109 patients were included, of whom 21.1% received CRCLM resection (R0=73.9%), with 57.7% having left-sided colon cancer (LCC) and 42.2% having right-sided colon cancer (RCC). SM predominated (69.7%). The median duration of follow-up was 21,3 months (95%CI=15,4-25,2). ≥5 hepatic metastases prevailed in the SM group (N=61; 83.5%). 21% of all patients underwent CRCLM resection (R0=78.2%). We observed a double rate of patients unresponsive to standard systemic antineoplastic treatments in the SM group (35.8% vs. 17.9% of the MM group) (p=0.27). We found a significantly longer median overall survival (OS) in patients with MM-LCC compared with the other groups (27.7 months; HR=0.3797; 95%CI=0.19-0.74; p=0.0205). The median OS, regardless of PTL, was higher in the MM group (16,5 months vs. 16,1 months; HR=0,29; 95%CI=0,13-0,67; p=0.0038) as well as progression-free survival (PFS) (11 months vs. 10,2 months; HR=0,61; 95%CI=0,33-1,12; p=0.11). Finally, in patients undergoing liver surgery, a noteworthy median OS was shown to be significantly in favor of patients with metachronous liver metastases from the primary left tumor (37.0 months; HR=0.47; 95%CI=0.11-1.96; p=0.0041). Conclusions Our real-life study demonstrated that patients with LCC, particularly MM-LCC, have the highest survival and that the timing of CRCLM should be a prognostic factor.
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Background: There is no clear information on the proportion of patients who need therapy for immune-related thyroid dysfunction (irTD) or who need to delay, omit, or discontinue immunotherapy. Furthermore, it is not well known whether irTD correlates with better outcomes or not. Patients and Methods: We conducted a retrospective study in patients with metastatic non-small cell lung cancer (NSCLC) treated with anti-PD1 or anti-PD-L1. Results: Our study enrolled 75 patients, 25.3% of them developed immune-related thyroid dysfunction. Three patients delayed a course of immunotherapy due to irTD, 2 patients omitted a course and 1 patient permanently discontinued. In patients with irTD compared with those without irTD the ORR was 42.1% vs. 7.1% (p<0.001), DCR was 78.9% vs. 32.1% (p<0.001); mPFS was 15.7 vs. 3.6 months (p<0.001) and mOS was 18.6 months vs. 5.1 months (p<0.001). Conclusion: Immune-related thyroid dysfunction has a mild impact on the immunotherapy treatment program. The occurrence of irTD correlates with more favorable response and survival.
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BACKGROUND: The adaptive immune response following COVID-19 vaccination is essential for humoral immunogenicity and clinical protection against symptomatic infections. We present the results of circulating lymphocyte profiling and their correlation with antibody response in cancer patients tested serologically six months after receiving a two-dose schedule of mRNA-BNT162b2 vaccine. METHODS: Absolute counts of lymphocyte subsets were determined using peripheral blood immunophenotyping. We collected samples for flow cytometry analysis alongside quantitative detection of IgG antibodies against the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein (S1). An IgG titer ≥ 50 AU/mL defined a positive seroconversion response. RESULTS: 311 patients were evaluable for lymphocyte profiling and serologic testing. A preliminary multivariate analysis revealed that cytotoxic chemotherapy was the most consistent factor associated with lower counts of all lymphocyte subpopulations. T helper and B cells were found to be useful in predicting the occurrence of a positive seroconversion response using ROC curve analysis. A significant positive linear correlation was shown when anti-RBD-S1 IgG titers were compared to these lymphocyte subset counts. Univariate analysis indicated that antibody titers and seroconversion rates were significantly improved in the high-level T and B cell subgroups. Multivariate analysis confirmed these significant interactions, as well as the negative predictive value of immunosuppressive corticosteroid therapy. CONCLUSIONS: These findings suggest that simple and widely available peripheral counts of T helper and B cells correlate with humoral response to mRNA-BNT162b2 vaccine in actively treated cancer patients. Upon validation, our results could provide additional insights into the predictive assessment of vaccination efficacy.
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Formación de Anticuerpos , Vacuna BNT162 , COVID-19 , Neoplasias , Anticuerpos Antivirales , Vacuna BNT162/inmunología , COVID-19/prevención & control , Humanos , Inmunoglobulina G , Subgrupos Linfocitarios , Linfocitos , SARS-CoV-2 , Glicoproteína de la Espiga del CoronavirusRESUMEN
BACKGROUND/AIM: Recent evidence suggests potential synergistic antitumor effects of the combination of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors with the oral hypoglycemic agent metformin. The aim of this study was to investigate the safety and activity of metformin combined with nivolumab in diabetic cancer patients. PATIENTS AND METHODS: Patients with advanced melanoma, renal cell carcinoma or lung cancer receiving nivolumab with concurrent diabetes treated with metformin were retrospectively collected. The primary endpoint was the safety of nivolumab plus metformin combination. RESULTS: We collected 40 patients with solid tumors who received metformin for concomitant diabetes and nivolumab as anticancer therapy in four Italian Hospitals. The concomitant use of nivolumab and metformin was well tolerated; adverse events (AEs) of any grade occurred in 75% of patients (mainly fatigue, pruritus, rash, and asthenia). Grade 3 AEs occurred only in 20% of cases; no grade 4 AEs were observed. A statistically significant correlation was found between higher doses of metformin (>1,000 mg daily) and longer progression-free survival (p=0.021), overall survival (p=0.037) and higher overall response rate. CONCLUSION: The combination of nivolumab and metformin was safe and might have an antitumor activity, supporting further investigations on the synergistic antitumor effect of this combination.
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Antígeno B7-H1/antagonistas & inhibidores , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Metformina/uso terapéutico , Neoplasias/tratamiento farmacológico , Nivolumab/uso terapéutico , Anciano , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidad , Femenino , Humanos , Hipoglucemiantes/efectos adversos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Italia , Masculino , Metformina/efectos adversos , Neoplasias/diagnóstico , Neoplasias/inmunología , Neoplasias/mortalidad , Nivolumab/efectos adversos , Supervivencia sin Progresión , Estudios Retrospectivos , Factores de TiempoRESUMEN
Hemangiopericytoma (HPC) is an uncommon perivascular tumor, first described in 1942, occurring most frequently in the extremities (pelvis, meninges, head and neck), and rarely affecting the urogenital system. In 1870, Wagner published the first histological description of a Solitary Fibrous Tumor (SFT) of the pleura. It is now thought that the majority of lesions previously called hemangiopericytomas (HPCs) are essentially indistinguishable from solitary fibrous tumors (SFTs). Nowadays, the new WHO classification of soft tissue tumors categorizes most HPCs as SFTs. We report the first case of penile SFT-HPC in a 44-year-old man, presenting with a 3-year history of slow-growing penile mass. The patient underwent a tumor excision. Six months after surgery he is free of local recurrence and distant metastasis.
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Hemangiopericitoma/diagnóstico por imagen , Hemangiopericitoma/cirugía , Neoplasias del Pene/diagnóstico por imagen , Neoplasias del Pene/cirugía , Tumores Fibrosos Solitarios/diagnóstico por imagen , Tumores Fibrosos Solitarios/cirugía , Adulto , Humanos , Masculino , Resultado del Tratamiento , Procedimientos Quirúrgicos Urológicos Masculinos/métodosRESUMEN
The purpose of this study was to evaluate the efficacy of somatostatin receptor scintigraphy (SRS) in imaging metastases in patients with advanced breast cancer (BC), and assess the relationship between exposure to chemotherapy and hormonotherapy with overexpression of somatostatin receptor (SS-R) on the breast cancer cell surface. Twelve patients with metastatic breast cancer were intravenously (i.v.) injected with In-111 pentatreotide (120 MBq). Early and later images were obtained with a double-head gamma camera equipped with medium-energy collimators. SPECT was performed when needed. Imaging results were compared with computed tomography and bone scan. Uptake levels were evaluated by site-specific visual analysis. Metastatic breast cancer can be visualized with SRS. Global sensitivity of imaging was 80% and specificity for correct prediction of tumor absence was 100%. Sensitivity was significantly higher for bone and lung metastases. SRS results related to the expression of SS-R on metastatic cell surfaces did not evidence a relationship with the biologic characteristics of the primary BC and drug exposure. In our series, SRS quantitative analysis demonstrated that tumor metastases differ greatly in uptake levels. Fifteen percent of metastatic sites in our series showed strong uptake. Our data support the important specificity of SRS in identifying BC metastases, mostly in cases of bone and lung disease, as well as the role of SRS in predicting responsiveness of metastatic BC cells to treatment with somatostatin analogues (SS), when SS-Rs are overexpressed on cell surfaces. If our results are confirmed in large scale studies, SRS shows the potential to treat selected patients with overexpressed SS-R on their tumoral cells with designed target therapies with SS analogue.
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Neoplasias de la Mama/diagnóstico por imagen , Neoplasias de la Mama/patología , Receptores de Somatostatina/análisis , Somatostatina/análogos & derivados , Adolescente , Adulto , Anciano , Neoplasias Óseas/diagnóstico por imagen , Neoplasias Óseas/secundario , Femenino , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/secundario , Persona de Mediana Edad , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
Neoadjuvant chemotherapy (NACT) is the treatment of choice in patients (pts) with locally advanced (LABC) and inflammatory breast cancer (IBC). To evaluate the role of Tc-99m sestamibi imaging in the prediction of response to NACT and in the in vivo functional detection of intrinsic or acquired chemoresistance, 24 female pts with LABC (n=21) or IBC (n=3) were prospectively studied. Tc-99m scintimammography was performed 1-3 days before treatment (first) and 2-5 days after the completion (second) of NACT (epirubicin and cyclophosphamide for LABC and doxorubicin and vinorelbine for IBC). Three planar images (2 lateral prone and one anterior supine, 10 min/each) were obtained 10 min postinjection and a lateral prone image (10 min) of the affected breast (B) was obtained at 4 h. To calculate the tumor to normal B ratio (TBR), 2 identical irregular regions of interest (ROIs) were drawn around the tumor (T) and in adjacent ipsilateral normal B on both early (E) and delayed (D) prone lateral images. The TBR was obtained as the ratio of the mean counts per pixels in the 2 ROIs. Then Tc-99m sestamibi retention index (RI) in the T was determined by dividing the D-TBR by the E-TBR. Afterwards, NACT response was assessed pathologically or clinically in inoperable disease. Scintigraphic sensitivity for correct prediction of T presence after NACT was 81% (17/21), whereas specificity for correct prediction of T absence was 100% (3/3). In LABC, 3 patients had a pathological complete response: first RI was high (>0.56) in all 3, while no T uptake was visible on the second scintigraphy. Eighteen patients did not show a pathological complete response: in 5, both first and second RI were low (=0.56); 9 had high first RI but low second; 4 had high first RI and no T detected on the second scan. In IBC, the only patient with a clinical complete response had both first and second RI high, whereas the 2 non-responsive pts had both first and second RI low. These results indicate that Tc-99m sestamibi scintimammography can predict LABC and IBC response to NACT. The scintigraphy protocol, including 2 studies before and after NACT, is useful for detecting intrinsic and acquired chemoresistant BC in vivo, which is important for planning therapy and predicting prognosis.