Effect of internal port on dose distribution in post-mastectomy radiotherapy for breast cancer patients after expander breast reconstruction.

Background: In patients with expander-based reconstruction a few dosimetric analyses detected radiation therapy dose perturbation due to the internal port of an expander, potentially leading to toxicity or loss of local control. This study aimed at adding data on this field. Materials and methods: A dosimetric analysis was conducted in 30 chest wall treatment planning without and with correction for port artifact. In plans with artifact correction density was overwritten as 1 g/cm3. Medium, minimum and maximum chest wall doses were compared in the two plans. Both plans, with and without correction, were compared on an anthropomorphic phantom with a tissue expander on the chest covered by a bolus simulating the skin. Ex vivo dosimetry was carried out on the phantom and in vivo dosimetry in three patients by using film strips during one treatment fraction. Estimated doses and measured film doses were compared. Results: No significant differences emerged in the minimum, medium and maximum doses in the two plans, without and with correction for port artifacts. Ex vivo and in vivo analyses showed a good correspondence between detected and calculated doses without and with correction. Conclusions: The port did not significantly affect dose distribution in patients who will receive post-mastectomy radiation therapy.

Novel Harmonization Method for Multi-Centric Radiomic Studies in Non-Small Cell Lung Cancer.

The purpose of this multi-centric work was to investigate the relationship between radiomic features extracted from pre-treatment computed tomography (CT), positron emission tomography (PET) imaging, and clinical outcomes for stereotactic body radiation therapy (SBRT) in early-stage non-small cell lung cancer (NSCLC). One-hundred and seventeen patients who received SBRT for early-stage NSCLC were retrospectively identified from seven Italian centers. The tumor was identified on pre-treatment free-breathing CT and PET images, from which we extracted 3004 quantitative radiomic features. The primary outcome was 24-month progression-free-survival (PFS) based on cancer recurrence (local/non-local) following SBRT. A harmonization technique was proposed for CT features considering lesion and contralateral healthy lung tissues using the LASSO algorithm as a feature selector. Models with harmonized CT features (B models) demonstrated better performances compared to the ones using only original CT features (C models). A linear support vector machine (SVM) with harmonized CT and PET features (A1 model) showed an area under the curve (AUC) of 0.77 (0.63-0.85) for predicting the primary outcome in an external validation cohort. The addition of clinical features did not enhance the model performance. This study provided the basis for validating our novel CT data harmonization strategy, involving delta radiomics. The harmonized radiomic models demonstrated the capability to properly predict patient prognosis.

Stereotactic radiotherapy for lung oligometastases.

30-60% of cancer patients develop lung metastases, mostly from primary tumors in the colon-rectum, lung, head and neck area, breast and kidney. Nowadays, stereotactic radiotherapy (SRT ) is considered the ideal modality for treating pulmonary metastases. When lung metastases are suspected, complete disease staging includes a total body computed tomography (CT ) and/or positron emission tomography-computed tomography (PET -CT ) scan. PET -CT has higher specificity and sensitivity than a CT scan when investigating mediastinal lymph nodes, diagnosing a solitary lung lesion and detecting distant metastases. For treatment planning, a multi-detector planning CT scan of the entire chest is usually performed, with or without intravenous contrast media or esophageal lumen opacification, especially when central lesions have to be irradiated. Respiratory management is recommended in lung SRT, taking the breath cycle into account in planning and delivery. For contouring, co-registration and/or matching planning CT and diagnostic images (as provided by contrast enhanced CT or PET-CT ) are useful, particularly for central tumors. Doses and fractionation schedules are heterogeneous, ranging from 33 to 60 Gy in 3-6 fractions. Independently of fractionation schedule, a BED10 > 100 Gy is recommended for high local control rates. Single fraction SRT (ranges 15-30 Gy) is occasionally administered, particularly for small lesions. SRT provides tumor control rates of up to 91% at 3 years, with limited toxicities. The present overview focuses on technical and clinical aspects related to treatment planning, dose constraints, outcome and toxicity of SRT for lung metastases.

The NIPRO Study: An Observational, Retrospective, Multicenter Study on the Safety of the Radiotherapy and Immunotherapy Combination for Advanced-Stage NSCLC.

INTRODUCTION: In this observational, retrospective, multicenter study, we aimed to assess the safety of the combination of local metastasis-directed radiotherapy (RT) and immunotherapy (IT) in a cohort of advanced non-small-cell lung cancer (aNSCLC) patients. MATERIAL AND METHODS: We collected clinical data of aNSCLC patients who received concomitant RT and anti-PD-1/PD-L1 inhibitors in seven Italian centers from September 2015 to June 2019. Concomitant RT was defined as delivered ≤4 weeks before or after the first or last administration of immunotherapy, or within two consecutive cycles of ICI. All adverse events apparently related to RT and/or IT were graded according to the Common Terminology Criteria for Adverse Events, version 4.0, and reported in terms of incidence and severity as immune related or RT related, or combined. RESULTS: We analyzed the clinical charts of 187 patients. Median follow-up time was 23 months, and median overall survival was 16.5 months (range, 3-162). Thirteen patients developed pure RT-related side effects, and 43 patients (23.9%) developed immune-related side effects. No additive toxic effects were observed. A case of grade 5 pulmonary toxicity was recorded as a possible consequence of a combined effect. CONCLUSION: This analysis suggests that the combination of concomitant RT and anti-PD-1/PD-L1 agents is safe, and the two toxicity profiles are independent.

Pulmonary function in stereotactic body radiotherapy with helical tomotherapy for primary and metastatic lung lesions.

AIMS: This retrospective study reports outcomes after stereotactic body radiation therapy (SBRT) as delivered by helical tomotherapy (HT) for lung lesions. It promotes a dose escalation program. METHODS: Histological and/or radiological findings and/or case histories identified 41 primary and 15 metastatic lesions. Thirty patients received 40 Gy in 5 fractions (BED 72 Gy10Gy) and 26 50 Gy in 5 fractions (BED 100Gy10Gy). Primary end point was lung toxicity. Secondary end points were respiratory function, local control and local progression-free survival. RESULTS: Acute toxicity developed in 18/56 patients and late toxicity in 8/54. Median FEV-1 variations versus baseline were - 0.5% (range - 16 to + 43%) at 6 months and - 4.00% (range - 42 to + 18%) at 24 months. Median DLCO variations versus baseline were - 1% (range - 38 to + 36%) at 6 months and - 12.2% (range - 48 to + 11%) at 24 months. At 6 months, a significant positive correlation emerged between FEV-1 change and KPS (p = 0.047). At 24 months, a significant negative correlation emerged between FEV-1 change and the ipsilateral lung V5 (p = 0.006). A low baseline DLCO correlated with more marked DLCO worsening at 6 months (p = 0.012). At 24 months, DLCO worsening correlated significantly with the median contralateral lung dose (p = 0.003). At the last checkup, 23 patients were in complete remission, 16 were in partial remission, 5 had stable disease, and 7 were in relapse. Median follow-up was 12 months (range 5-56). CONCLUSIONS: In patients with lung disease, SBRT, as delivered by HT, was well tolerated and provided good local control.

Chemoradiotherapy with temozolomide after high-dose methotrexate for primary CNS lymphoma: a multicenter phase I study of a response-adapted strategy.

This study aimed to define the maximum tolerated dose (MTD) of temozolomide (TMZ) concurrent with radiotherapy (RT) after high-dose methotrexate (HD-MTX) for newly diagnosed primary central nervous system lymphoma (PCNSL). Adult patients with PCNSL were treated according to a response-adapted strategy. HD-MTX (3.5 g/m2) was followed by concomitant RT and escalating TMZ (50-60-75 mg/m2/day, 5 days/week). The total radiation dose was modulated according to the patient's response to HD-MTX. All patients received 30 Gy to the whole brain plus leptomeninges to C2, including the third posterior of the orbital cavity (clinical target volume 2; CTV2), plus 6, 10, or 16 Gy to the primary site, including the residual mass (CTV1), if a complete response (CR), partial response (PR)/stable disease (SD), or progressive disease (PD) was observed, respectively. Acute toxicities were graded according to the RTOG-EORTC criteria. Dose-limiting toxicity (DLT) was defined as grade 4 hematological toxicity or grade 3-4 hepatic toxicity, although 75 mg/m2/day was the maximum dose regardless of DLT. Neurocognitive function was evaluated using the Mini-Mental State Examination. Three patients were enrolled at each TMZ dose level (total = 9 patients). Twelve lesions were treated. Six patients received 2 cycles of HD-MTX, while 3 received only 1 cycle because of hepatic or renal toxicity. All patients completed chemoradiotherapy without interruptions. No DLT events were recorded. TMZ appears to be tolerable at a dose of 75 mg/m2/day when administered concomitantly with radiotherapy and after HD-MTX.

Helical tomotherapy re-irradiation for patients affected by local radiorecurrent prostate cancer.

BACKGROUND: Salvage re-irradiation in patients affected by radiorecurrent prostate cancer might be a valid as well as challenging treatment option. The aim of this study was to evaluate feasibility and toxicity of salvage external beam radiotherapy (EBRT) re-treatment in patients affected by radiorecurrent prostate cancer within the prostate gland or the prostate bed. MATERIALS AND METHODS: 15 patients underwent EBRT re-treatment using helical tomotherapy (HT), with daily Megavolt computed tomography image-guidance. We registered toxicity according to Common Terminology Criteria for Adverse Events (CTCAE) v4.0. Biochemical relapse was defined as a PSA increase > 20% compared with the pre-EBRT re-treatment value. Survival curves were calculated using the Kaplan-Meier method. RESULTS: All patients received a total dose of 50 Gy (25 × 2 Gy), and 7 (46.6%) had concomitant androgen deprivation therapy (median duration of 12 months). With a median follow-up of 40.9 months, the 2-year and 4-year biochemical relapse-free survival were 55% and 35%, respectively. Acute and late genito-urinary (GU) toxicity ≥2 were recorded in 4 (26.6%) and 5 (33.3%) patients, respectively, and the 4-year late GU toxicity was 30%. Acute gastrointestinal toxicity ≥2 was recorded in 2 (13.3%) cases, whereas no patient experienced late toxicity. CONCLUSIONS: Despite the inherent bias of a retrospective analysis, our long-term results showed a low toxicity profile with a relatively low rate of biochemical control for HT re-treatment in patients affected by local radiorecurrent prostate cancer. Prospective trials are needed to investigate the role of EBRT in this setting.

Potential skin morbidity reduction with intensity-modulated proton therapy for breast cancer with nodal involvement.

Background: Different modern radiation therapy treatment solutions for breast cancer (BC) and regional nodal irradiation (RNI) have been proposed. In this study, we evaluate the potential reduction in radiation-induced skin morbidity obtained by intensity modulated proton therapy (IMPT) compared with intensity modulated photon therapy (IMXT) for left-side BC and RNI. Material and Methods: Using CT scans from 10 left-side BC patients, treatment plans were generated using IMXT and IMPT techniques. A dose of 50 Gy (or Gy [RBE] for IMPT) was prescribed to the target volume (involved breast, the internal mammary, supraclavicular, and infraclavicular nodes). Two single filed optimization IMPT (IMPT1 and IMPT2) plans were calculated without and with skin optimization. For each technique, skin dose-metrics were extracted and normal tissue complication probability (NTCP) models from the literature were employed to estimate the risk of radiation-induced skin morbidity. NTCPs for relevant organs-at-risk (OARs) were also considered for reference. The non-parametric Anova (Friedman matched-pairs signed-rank test) was used for comparative analyses. Results: IMPT improved target coverage and dose homogeneity even if the skin was included into optimization strategy (HIIMPT2 = 0.11 vs. HIIMXT = 0.22 and CIIMPT2 = 0.96 vs. CIIMXT = 0.82, p < .05). A significant relative skin risk reduction (RR = NTCPIMPT/NTCPIMXT) was obtained with IMPT2 including the skin in the optimization with a RR reduction ranging from 0.3 to 0.9 depending on the analyzed skin toxicity endpoint/model. Both IMPT plans attained significant OARs dose sparing compared with IMXT. As expected, the heart and lung doses were significantly reduced using IMPT. Accordingly, IMPT always provided lower NTCP values. Conclusions: IMPT guarantees optimal target coverage, OARs sparing, and simultaneously minimizes the risk of skin morbidity. The applied model-based approach supports the potential clinical relevance of IMPT for left-side BC and RNI and might be relevant for the setup of cost-effectiveness evaluation strategies based on NTCP predictions, as well as for establishing patient selection criteria.

Acute Toxicity Profiles of Hypofractionated Adjuvant and Salvage Radiation Therapy After Radical Prostatectomy: Results of a Prospective Study.

PURPOSE: Hypofractionated radiation therapy (RT) is controversial after radical prostatectomy (RP). In this interim analysis, our prospective observational study assessed acute genitourinary (GU) and gastrointestinal (GI) toxicity after hypofractionated adjuvant and salvage RT, as delivered by helical tomotherapy (HT), in patients with prostate cancer. METHODS AND MATERIALS: After undergoing RP with or without pelvic lymph node dissection, 112 patients were enrolled. Hypofractionated adjuvant RT (2.25 Gy daily for 29 fractions; total 65.25 Gy) was administered to 40 patients with high-risk features. Hypofractionated salvage RT (2.25 Gy daily for 32 or 33 fractions; total 72-74.25 Gy) was prescribed for 72 patients (24 with biochemical relapse, 48 with local relapse). Toxicity was graded according to the Common Terminology Criteria for Adverse Events version 4.02. The impact of RT on urinary flow was assessed by uroflowmetry. RESULTS: Acute GU toxicity occurred in 41 of 112 patients (36%) (G1 31, G2 10). Acute GI toxicity was observed in 55 (49%) patients (G1 44, G2 11). Uroflowmetry showed that only salvage RT reduced maximum flow significantly (maximum, 68 vs 50 mL/s; P = .003), perhaps because a higher RT dose had been administered. CONCLUSIONS: After RP, moderate hypofractionated adjuvant and salvage RT were associated with acceptable incidences of slight-to-moderate acute GU and GI toxicity and had little impact on urinary flow. Prospective trials are warranted with longer follow-up in larger cohorts to confirm these findings.

Hypofractionated whole breast radiotherapy with or without hypofractionated boost in early stage breast cancer patients: a mono-institutional analysis of skin and subcutaneous toxicity.

BACKGROUND: Our study evaluated skin and subcutaneous toxicity analyzing its correlation with patient- and treatment-related factors in a large mono-institutional series of women with early stage breast cancer treated with adjuvant hypofractionated whole breast radiotherapy (WBRT) with or without a sequential hypofractionated boost (HB). METHODS: Two hundred and nineteen patients, median age 62 years, received adjuvant hypofractionated WBRT in 16 fractions to a total dose of 42.4 Gy. Patients with negative prognostic factors received a HB of 2.65 Gy for 4 or 5 (patients with focal positive surgical margins) fractions. Systemic adjuvant treatments were hormonal therapy (HT) and/or chemotherapy (CHT) and/or Trastuzumab. Toxicities were assessed using the Common Terminology Criteria for Adverse Events (CTCAE 4.03) scale at 5th, 10th, 16th, 20th day from the start of radiotherapy (RT) and 1, 6 and 12 months after the end of RT. Univariate and multivariate analysis estimated toxicity predictive factors. RESULTS: No case of treatment interruption and no acute or late G3 toxicities occurred. In the univariate analysis HB administration resulted a risk factor for acute toxicity, while CHT administration and number of excised lymph nodes ≥ 10 resulted a risk factor for late toxicity. In the multivariate analysis none of the evaluated factors emerged a risk factor for acute and/or late toxicity. CONCLUSIONS: Our results confirmed that hypofractionated WBRT even followed by a HB resulted safe and well tolerated. Longer follow-up is warranted to estimate late toxicity and treatment outcomes.

Skin toxicity after chest wall/breast plus level III-IV lymph nodes treatment with helical tomotherapy.

INTRODUCTION: To evaluate the incidence of toxicity in breast cancer with helical tomotherapy (HT). MATERIALS AND METHODS: 51 patients with breast cancer were assigned to postoperative radiotherapy by means of HT to the chest wall/breast plus draining nodes. During HT treatment, toxicity was monitored and were assessed using the Common Terminology Criteria for Adverse Events 4.0 scale. RESULTS: Acute skin G3 toxicity observed in 1.9% cases. No acute or late G4 toxicity was observed. At a median follow-up of 21 months 2 patients have late G1 toxicity. CONCLUSIONS: HT was associated with a low incidence of low-grade skin toxicity.

Comparing four radiotherapy techniques for treating the chest wall plus levels III-IV draining nodes after breast reconstruction.

OBJECTIVE: To compare the dosimetric outcomes of four radiotherapy (RT) techniques for treating the chest wall plus draining nodes after mastectomy and breast reconstruction. METHODS: Three-dimensional conformal radiotherapy, linac-based intensity modulated RT, helical tomotherapy (HT) and direct tomotherapy treatments were planned for 40 breast cancer patients. Dose prescription was 50 Gy. Plans were compared in terms of doses to the planning target volume, organs at risk and the homogeneity index. The non-parametric Friedman test for paired data and the Conover post hoc analysis were used for data analysis. RESULTS: HT provided the highest D90 and D98% and the lowest HI, V107% and D2%. HT was associated with the lowest D2% and V25 Gy to the heart in left-sided treatments but the mean cardiac dose was highest. HT provided the highest V5 Gy and V20 Gy to the ipsilateral lung, but the V30 Gy was lower. The contralateral breast and lung were more exposed with HT. CONCLUSION: The present dosimetric study together with daily use of CT-MV image guided RT have led us to opt for HT after mastectomy and breast reconstruction and to draw up a suitable protocol for treating the chest wall and levels III and IV draining nodes. Advances in knowledge: HT is a suitable for treating the chest wall and levels III and IV draining nodes.

Comparison of Helical Tomotherapy and Direct Tomotherapy in Bilateral Whole Breast Irradiation in a Case of Bilateral Synchronous Grade 1 and Stage 1 Breast Cancer.

BACKGROUND Synchronous bilateral breast cancer is rare. A case is presented where whole breast irradiation (WBI) was planned after breast conserving surgery in a patient with synchronous bilateral breast cancer. A comparison was made between the feasibility of helical tomotherapy and direct tomotherapy. CASE REPORT A 60-year-old woman was found to have bilateral breast nodules on routine mammographic screening, resulting in bilateral lumpectomy and sentinel lymph node biopsy. Histopathology showed a 6 mm diameter invasive ductal carcinoma in the right breast (Grade 1, hormone receptor positive, HER2 negative) and an 8mm diameter tubular carcinoma in the left breast (Grade 1, hormone receptor positive, HER2 negative). Lymph node biopsy and histology, chest X-ray, abdominal ultrasound scan, and bone scintigraphy were negative for metastases (both tumors were Stage 1). Adjuvant therapy with commenced with anastrozole, but no chemotherapy was given. Clinical target volumes (CTVs) were contoured on computed tomography (CT) images. For planning target volumes (PTVs), CTVs were expanded by 1 cm in all directions, except for the medial 5 mm. Since dose constraints to organs at risk (OARs) were beyond established limits, CTVs were expanded by 5 mm. For PTVs, OAR doses and homogeneity indices for helical tomotherapy and direct tomotherapy were compared. Helical tomotherapy provided better target volume coverage and OAR sparing than direct tomotherapy. CONCLUSIONS In a case of bilateral synchronous Stage 1 and Grade 1 breast cancer, helical tomotherapy appeared more suitable than direct tomotherapy.

Statins Protect Against Acute RT-related Rectal Toxicity in Patients with Prostate Cancer: An Observational Prospective Study.

AIM: To analyze risk factors for acute rectal toxicity during hypofractionated intensity-modulated radiotherapy (IMRT) for prostate cancer. PATIENTS AND METHODS: A total of 195 patients received 74.25 Gy in 33 fractions to the prostate and, if involved, to the seminal vescicles (SV). When the risk of SV involvement was >15% according to the Roach's formula, they received 62 Gy in 33 fractions. Overall, 107/195 patients (54.87%) received hormonal therapy (luteinizing hormone-releasing hormone analogue, anti-androgen, or both). Common Terminology Criteria for Adverse Events version 3.0 was used to classify rectal toxicity. RESULTS: Acute rectal toxicity occurred in 79 (40.51%) patients (grade 1 in 44). In univariate analysis, use of calcium channel blockers significantly reduced the acute rectal toxicity rate and 3-hydroxy-methylglutaryl CoA reductase inhibitors (statins) significantly reduced the rectal toxicity rate and grade. In multivariate analysis, only statin use was an independent protective factor. CONCLUSION: In patients with prostate cancer treated with a moderate hypofractionated IMRT schedule, use of statins lowered the incidence and grade of acute rectal toxicity.

Treatment outcomes and patterns of radiologic appearance after hypofractionated image-guided radiotherapy delivered with helical tomotherapy (HHT) for lung tumours.

OBJECTIVE: To evaluate treatment outcomes and patterns of CT lung injury after hypofractionated image-guided radiotherapy delivered with helical tomotherapy (HHT) in a series of inoperable lung lesions. METHODS: 68 patients who were medically inoperable (69 lesions) without evidence of viable extrathoracic disease were included. Dose prescription was driven by tumour location (hilar/pericentral vs peripheral) and/or target volume. 52% of the lesions received a biological equivalent dose (BED10) ≥100 Gy. Assessment of tumour response was based on the Response Evaluation Criteria in Solid Tumours 1.1 criteria coupled with fluorine-18 fludeoxyglucose/positron emission tomography-CT. Toxicity monitoring was focused on treatment-related pulmonary adverse events according to the Common Terminology Criteria for Adverse Events v. 4.0. Acute and late events were classified as radiation pneumonitis (RP) and radiation fibrosis (RF), respectively. Survival curves were calculated using the Kaplan-Meier method. Univariate and multivariate analyses of survival were performed using the Cox proportional hazards model. RESULTS: After a median follow-up of 12 months (range, 3-31 months), no instances of ≥Grade 4 RP was documented, and clinically severe (Grade 3) RP occurred in 5.8% of the patients. 2 (3%) patients developed a late severe (≥Grade 3) symptomatic RF. No specific pattern of CT lung injury was demonstrated, in both acute and late settings. Median overall survival (OS) and progression-free survival (PFS) for the entire population were 30.8 and 14.1 months, respectively. At multivariate analysis (MVA), BED10 ≥ 100 Gy and KPS ≥ 90 emerged as significant prognostic factors for OS (p = 0.01 and p = 0.001, respectively), and BED10 ≥ 100 Gy for PFS (p = 0.02). CONCLUSION: Our findings show that HHT adjusted for tumour location and/or target volume is an effective treatment with an acceptable toxicity profile in patients who are medically inoperable with lung tumours and is not associated with a specific pattern of lung injury. Therefore, it can represent a viable option when conventional stereotactic ablative radiotherapy facilities are not available. Advances in knowledge: The present study is among the largest series addressing the role of HHT for inoperable lung tumours. This technique is safe and effective and is not associated with a specific pattern of lung injury, at least at early and average time points.

Helical tomotherapy for duodenal adenocarcinoma in an elderly patient: A case report.

To evaluate the efficacy and feasibility of external beam radiotherapy (EBRT) for duodenal adenocarcinoma in an 84-year-old female who underwent EBRT (2.2 Gy/d for a total dose of 46.2 Gy) using helical tomotherapy (HT). Toxicity was evaluated on the National Cancer Institute's common toxicity criteria (CTCAE 3.0). The patient completed the treatment without G3-G4 toxicity. After 22-mo follow-up, she is alive and well, in complete remission with no late side effects. HT seems to be feasible and effective for duodenal adenocarcinoma in old to very old patients.

Sacrum colon-rectal cancer metastasis: microwave ablation for palliative pain treatment.

Local treatment of bone metastasis (BM) remains controversial in colon-rectum carcinoma for pain control. A patient developed a sacrum BM 4years after a left colectomy for an adenocarcinoma. Metastasis was treated in one session of CT-guided microwave ablation showing good pain control immediately after and on follow-up at four months.

The Total Body Irradiation Schedule Affects Acute Leukemia Relapse After Matched T Cell-Depleted Hematopoietic Stem Cell Transplantation.

PURPOSE: We sought to determine whether the total body irradiation (TBI) schedule affected outcome in patients with acute leukemia in complete remission who received T cell-depleted allogeneic hematopoietic stem cell transplantation from HLA identical siblings. METHODS AND MATERIALS: The study recruited 55 patients (median age, 48 years; age range, 20-66 years; 30 men and 25 women; 34 with acute myeloid leukemia and 21 with acute lymphoid leukemia). Hyperfractionated TBI (HTBI) (1.2 Gy thrice daily for 4 days [for a total dose of 14.4 Gy] from day -12 to day -9) was administered to 29 patients. Single-dose TBI (STBI) (8 Gy, at a median dose rate of 10.7 cGy/min on day -9) was given to 26 patients. RESULTS: All patients achieved primary, sustained engraftment with full donor-type chimerism. At 10 years, the overall cumulative incidence of transplant-related mortality was 11% (SE, ±0.1%). It was 7% (SE, ±0.2%) after HTBI and 15% (SE, ±0.5%) after STBI (P=.3). The overall cumulative incidence of relapse was 33% (SE, ±0.5). It was 13% (SE, ±0.5%) after HTBI and 46% (SE, ±1%) after STBI (P=.02). The overall probability of disease-free survival (DFS) was 59% (SE, ±7%). It was 67% (SE, ±0.84%) after HTBI and 37% (SE, ±1.4%) after STBI (P=.01). Multivariate analyses showed the TBI schedule was the only risk factor that significantly affected relapse and DFS (P=.01 and P=.03, respectively). CONCLUSIONS: In patients with acute leukemia, HTBI is more efficacious than STBI in eradicating minimal residual disease after HLA-matched T cell-depleted hematopoietic stem cell transplantation, thus affecting DFS.

Survival outcomes and incidence of brain recurrence in high-grade neuroendocrine carcinomas of the lung: Implications for clinical practice.

BACKGROUND: Among patients with advanced high-grade neuroendocrine carcinoma (HGNEC) of the lung, the optimal therapeutic management is much less established for large cell neuroendocrine carcinomas (LCNECs) than for small cell lung cancers (SCLCs). We evaluated the survival outcomes and incidence of brain recurrence of advanced LCNECs, and compared them with those of a population of SCLCs matched by stage. MATERIALS AND METHODS: Forty-eight unresected stage III HGNECs (16 LCNECs and 32 SCLCs) and 113 stage IV HGNECs (37 LCNECs and 76 SCLCs) were eligible for the analysis. The efficacy of platinum-etoposide chemotherapy with or without thoracic radiotherapy (TRT) and/or prophylactic cranial irradiation (PCI) was investigated. RESULTS: Overall response was significantly lower for LCNECs compared with SCLCs for both stage III (43.8% vs 90.6% respectively, P=0.004) and stage IV (43.3% vs 64.5%, respectively, P=0.04). Similarly, an inferior outcome was observed in terms of progression-free survival (PFS), and overall survival (OS) for LCNECs compared with SCLCs, which, however, reached significance only for stage III disease (median: 5.6 vs 8.9 months, P=0.06 and 10.4 vs 17.6 months, P=0.03 for PFS and OS, respectively). In the lack of PCI, LCNECs showed a high cumulative incidence of brain metastases, as 58% and 48% of still living stage III and IV patients, respectively, developed brain metastases at 18 months. CONCLUSION: Patients with advanced LCNECs are at high risk for brain recurrence. Unresected stage III LCNECs treated with platinum-etoposide with or without TRT bear a dismal prognosis, when compared indirectly with SCLC counterparts. Randomized trials should evaluate whether PCI could improve survival of advanced LCNECs.