Clinical feasibility and oncological safety of non-radioactive targeted axillary dissection after neoadjuvant chemotherapy in biopsy-proven node-positive breast cancer: a prospective diagnostic and prognostic study.

BACKGROUND: Targeted axillary dissection (TAD) includes biopsy of clipped lymph node and sentinel lymph nodes. However, clinical evidence regarding clinical feasibility and oncological safety of non-radioactive TAD in a real-world cohort remains limited. METHODS: In this prospective registry study, patients routinely underwent clip insertion into biopsy-confirmed lymph node. Eligible patients received neoadjuvant chemotherapy followed by axillary surgery. Main endpoints included the false-negative rate (FNR) of TAD and nodal recurrence rate. RESULTS: Data from 353 eligible patients were analyzed. After completion of neoadjuvant chemotherapy, 85 patients directly proceeded to axillary lymph node dissection (ALND), furthermore, TAD with or without ALND was performed in 152 and 85 patients, respectively. Overall detection rate of clipped node was 94.9% (95% CI, 91.3-97.4%) and FNR of TAD was 12.2% (95% CI, 6.0-21.3%) in our study, with FNR decreasing to 6.0% (95% CI, 1.7-14.6%) in initially cN1 patients. During a median follow-up of 36.6 months, 3 nodal recurrences occurred (3/237 with ALND; 0/85 with TAD alone), with a 3-year freedom-from-nodal-recurrence rate of 100.0% among the TAD-only patients and 98.7% among the ALND patients with axillary pathologic complete response ( P =0.29). CONCLUSIONS: TAD is feasible in initially cN1 breast cancer patients with biopsy-confirmed nodal metastases. ALND can safely be foregone in patients with negativity or a low volume of nodal positivity on TAD, with a low nodal failure rate and no compromise of 3-year recurrence-free survival.

Role of brachytherapy in post-operative cervical cancer patients with risk factors other than positive stump.

OBJECTIVE: This study aimed to determine the effectiveness of brachytherapy in post-operative cervical cancer patients with risk factors other than positive stump, and to identify the candidates most likely to benefit. METHODS: Newly diagnosed, non-metastatic cervical cancer patients treated in our hospital between January 2012 and November 2015 were retrospectively reviewed. Early stage patients receiving radical surgery and needing adjuvant external radiotherapy were included, but those with positive stump were excluded. All patients received external radiotherapy. They were divided into two groups: one group received vaginal brachytherapy and the other did not. The 5-year local-regional recurrence free survival (LRRFS) and overall survival (OS) rates in the two groups were compared. RESULTS: Two hundred and twenty-five patients were included in this study; while 99 received brachytherapy, 126 did not. The brachytherapy group had significantly superior 5-year LRRFS (87.7% vs. 72.5%, p = 0.004), but did not show a significant overall survival benefit (78.4% vs. 75.3%, p = 0.055). In multivariate analysis, brachytherapy, pathological type, high-risk factors, duration of radiotherapy, and transfusion were independent prognostic factors for 5-year LRRFS. In stratified analysis, the brachytherapy group showed superior LRRFS in those meeting Sedlis criteria (p = 0.017). CONCLUSION: The combination of external beam radiation therapy and brachytherapy can improve LRRFS in post-operative cervical cancer patients with risk factors other than positive stump. Therefore, brachytherapy should be considered for these patients.

Contouring the accessory parotid gland and major parotid glands as a single organ at risk during nasopharyngeal carcinoma radiotherapy.

Background and purpose: No research currently exists on the role of the accessory parotid gland (APG) in nasopharyngeal carcinoma (NPC). We thereby aimed to assess the effects of APG on the dosimetry of the parotid glands (PGs) during NPC radiotherapy and evaluate its predictive value for late xerostomia. Material and methods: The clinical data of 32 NPC patients with radiological evidence of the APG treated at Sun Yat-sen Memorial Hospital between November 2020 and February 2021 were retrospectively reviewed. Clinically approved treatment plans consisted of only the PGs as an organ at risk (OAR) (Plan1), while Plan2 was designed by considering the APG as a single organ at risk (OAR). The APG on Plan1 was delineated, and dose-volume parameters of the PGs alone (PG-only) and of the combined structure (PG+APG) were analyzed in both plans. The association of such dosimetric parameters in Plan1 with xerostomia at 6-9 months post-radiotherapy was further explored. Results: Fifty APGs were found, with a mean volume of 3.3 ± 0.2 ml. Significant differences were found in all dosimetric parameters between Plan1 and Plan2. The mean dose and percentage of OAR volumes receiving more than 30 Gy significantly reduced in Plan1 itself (PG-only vs. PG+APG, 39.55 ± 0.83 Gy vs. 37.71 ± 0.75 Gy, and 62.00 ± 2.00% vs. 57.41 ± 1.56%, respectively; p < 001) and reduced further in Plan2 (PG+APG, 36.40 ± 0.74 Gy, and 55.54 ± 1.61%, respectively; p < 0.001). Three additional patients met the dose constraint in Plan1, which increased to seven in Plan2. With APG included, the predictive power of the dosimetric parameters for xerostomia tended to improve, although no significant differences were observed. Conclusion: APG is anatomically similar to the PGs. Our findings suggest the potential benefits of treating the APG and PGs as a single OAR during radiotherapy (RT) of NPC by improving PG sparing.

Enhanced Efficacy of Neoadjuvant Chemotherapy with Nab-Paclitaxel and Platinum for Locally Advanced Cervical Cancer.

PURPOSE: We aimed to determine the effect of neoadjuvant chemotherapy consisting of albumin-bound paclitaxel ("nab-paclitaxel") and platinum (NACT-nPP) in patients with locally advanced cervical cancer (LACC). METHODS: Consecutive patients with newly diagnosed, non-metastatic LACC were recruited retrospectively between October 2016 and June 2020 in our hospital. All patients received concurrent chemoradiotherapy (CCRT) alone or neoadjuvant chemotherapy. We compared the complete response (CR) rate and 2-year progression-free survival (PFS) between patients receiving NACT-nPP and not receiving regimens or other regimens of neoadjuvant chemotherapy. RESULTS: A total of 195 patients were enrolled (78 in the NACT-nPP group and 117 in the control group). Upon chemoradiotherapy completion, 72 (92.3%) patients in the NACT-nPP group and 96 (82.1%) patients in the other group achieved CR (P = 0.042). For patients with squamous cell carcinoma, the NACT-nPP group had superior 2-year PFS than that of the control group (89.7% vs 74.1%, P = 0.027, HR = 2.486, 95% CI = 1.077-5.739) whereas for adenocarcinoma, 2-year PFS was 37.5% and 36.5%, respectively (P = 0.863). In multivariate analysis, NACT-nPP and stage were independent prognostic factors (P = 0.046 and 0.012, HR = 2.357 and 2.499, 95% CI = 1.016-5.465 and 1.216-4.930, respectively). The acute hematological adverse events above grade 3 were manageable in the NACT-nPP group (46.2%, 36/78), and the rate was lower than that in the control group (55.6%, 65/117). CONCLUSION: Compared with CCRT alone, NACT-nPP followed by CCRT could improve the CR rate and 2-year PFS of patients with locally advanced cervical squamous cell carcinoma, and the toxicity was tolerable. NACT-nPP was an independent prognostic factor for 2-year PFS. However, further prospective studies are needed to confirm our results.

Risk and mechanism of glucose metabolism disorder in the offspring conceived by female fertility maintenance technology.

Although female fertility maintenance technology (FFMT) provides an effective option for preserving fertility in patients with cancer suffering from fertility loss due to cancer treatment, previous studies have shown that the technique has certain potential risks and requires an assessment of the health status of the offspring since FFMT may lead to glucose metabolism disorder in offspring mice. The present animal study examined the glucose metabolism of adult mice offspring born from ovarian tissue cryopreservation and orthotopic allotransplantation. The mice were divided into three groups: normal, fresh ovary transplantation, and cryopreserved ovary transplantation. We recorded fasting blood glucose, glucose tolerance, and fasting serum insulin level for six months. Liver DNA, RNA, and proteins were extracted to detect the interaction between DNA methylation and Grb10 expression and insulin signaling pathway factors such as P-IGF1R, P-IRS2, P-AKT, and Grb10. Female recipient mice that received FFMT could successfully give birth after mating. The average litter size and total litter size of the cryopreserved and fresh groups showed marked differences compared with the normal group. Compared with the normal group, the fasting blood glucose and fasting serum insulin levels were higher in the cryopreserved and fresh groups. The mRNA and protein expressions of Grb10 were higher in the fresh and cryopreserved groups. Compared with the normal group, the DNA methylation status of four of the 11 sites of the Grb10 promoter was lower in the cryopreserved group. Grb10 overexpression inhibited the downstream phosphorylation protein factor expression (p-IGF-1R, p-IRS2, and p-Akt) of the IGF-1R signaling pathway. Female fertility maintenance technology (FFMT), including ovarian tissue cryopreservation (OTC), and orthotopic allotransplantation techniques might lead to glucose metabolism disorders in offspring mice.

Building radiation-resistant model in triple-negative breast cancer to screen radioresistance-related molecular markers.

BACKGROUND: To build the triple-negative breast cancer (TNBC) radiation resistance model in vitro and vivo, and screen the molecular markers that related to radiation resistance. METHODS: We used X-ray to irradiate MDA-MB-231 cells repeatedly to build radioresistant cell (231-RR), then select one gemcitabine-resistance of MDA-MB-231 cell (231-GEM). We screen differentially expressed genes of these cell lines. Then, we would select 2 genes of them associated with DNA damage repair or cell cycle, and build RNAi lentivirus vector to knock down related gene. We also used X-rays repeatedly exposure TNBC tumor xenograft to build tumor with radioresistance properties, and then verify previously screening differentially expressed genes using IHC. Finally, we used The Cancer Genome Atlas (TCGA) database to validate the relationships between radioresistance related genes and the prognosis of breast cancer. RESULTS: We got 161 up-regulated genes and 156 down-regulated genes from three cell lines. Cellular results show the 231-cell with knock-down CDKN1A or SOD2 gene, its radiation sensitivity was significantly enhanced. We successfully got the TNBC xenograft tumor with radioresistance properties. Immunohistochemical results show that the radioresistance of tumor tissue with higher p21 (CDKN1A encoding protein) and SOD2 expression (P<0.01). The prognosis of patients with low SOD2 expression is better than that of high expression, but have no statistical significance (P=0.119); patients with low CDKN1A expression is significantly better than high expression (P=0.000). Multivariate cox analysis manifest that CDKN1A gene expression level is an independent prognostic factor in breast cancer patient (P=0.008). CONCLUSIONS: Construction of radiation resistance cell and xenograft tumor with radio-resistant properties model for radiation biology research is feasible. High SOD2 and CDKN1A is associated with the poor prognosis in breast cancer patients. These two genes could be used as a predicted makers of breast cancer radiation sensitivity.

Grafted Neural Stem Cells Show Lesion-Specific Migration in Radiation-Injured Rat Brains.

Neural stem cells (NSCs) exhibit preferential homing toward some types of brain lesion, but their migratory property during radiation brain injury (RBI) remains unexplored. Here, we use the superparamagnetic iron oxide (SPIO)-labeled magnetic resonance imaging (MRI) technology to determine the migration of transplanted NSCs in two partial RBI models in real time, created by administering 30-55 Gy of radiation to the right or posterior half of the adult rat brain. SPIO-labeled NSCs were stereotactically grafted into the uninjured side one week after RBI. The migration of SPIO-labeled NSCs in live radiation-injured brains was traced by MRI for up to 28 days after engraftment and quantified for their moving distances and speeds. A high labeling efficiency (>90%) was achieved by incubating NSCs with 100µg/ml of SPIO for 12-24 hours. Upon stereotactic transplantation into the healthy side of the brain, SPIO-labeled NSCs were distinctively detected as hypointense signals on T2-weighted images (T2WI), showed sustained survival for up to 4 weeks, and exhibited directional migration to the radiation-injured side of the brain with a speed of 86-127 µm/day. The moving kinetics of grafted NSCs displayed no difference in brains receiving a high (55 Gy) vs. moderate (45 Gy) dose of radiation, but was slower in the right RBI model than in the posterior RBI model. This study shows that NSCs can be effectively labeled by SPIO and traced in vivo by MRI, and that grafted NSCs exhibit directional migration toward RBI sites in a route-dependent but radiation dose-independent manner.

Highlights on molecular targets for radiosensitization of breast cancer cells: Current research status and prospects.

In the past, searching for effective radiotherapy sensitization molecular targets and improving the radiation sensitivity of malignant tumors was the hot topic for the oncologists, but with little achievements. We will summarize the research results about breast cancer irradiation sensitization molecular targets over the past two decades; we mainly focus on the following aspects: DNA damage repair and radiation sensitization, cell cycle regulation and radiation sensitization, cell autophagy regulation and radiation sensitization, and radiation sensitivity prediction and breast cancer radiotherapy scheme making. And based on this summary, we will put forward some of our viewpoints.

Excessive Pretreatment Weight Loss Is a Risk Factor for the Survival Outcome of Esophageal Carcinoma Patients Undergoing Radical Surgery and Postoperative Adjuvant Chemotherapy.

Background: The prognostic values of weight loss and body mass index (BMI) in esophageal carcinoma remain controversial. This study aimed to evaluate the impacts of weight loss on the survival of patients undergoing radical surgery and adjuvant chemotherapy. Methods: The medical records of 189 consecutive patients with nonmetastatic esophageal carcinoma treated in our hospital between January 2012 and December 2013 were reviewed, and 121 patients were included for analysis. Results: Kaplan-Meier analysis revealed that the 3-year overall survival rate was significantly higher in the low pretreatment weight loss (pre-LWL) group than in the high pretreatment weight loss (pre-HWL) group (P < 0.001). In addition, the 3-year overall survival rate of normal weight group was higher than that of overweight and underweight groups (P = 0.007). Multivariate Cox proportional hazards analysis showed that pre-LWL group had a significantly better 3-year overall survival than pre-HWL group (P = 0.027, HR = 1.89, and 95% CI = 1.07-3.32). pN stage and age were also the survival prognostic factors. Conclusions: Our study showed that low pretreatment weight loss predicted a better survival outcome in the esophageal carcinoma patients with radical surgery and adjuvant chemotherapy. However, BMI and weight loss during treatment had no impact on the survival outcome.

Prognostic factors in breast phyllodes tumors: a nomogram based on a retrospective cohort study of 404 patients.

The aim of this study was to explore the independent prognostic factors related to postoperative recurrence-free survival (RFS) in patients with breast phyllodes tumors (PTBs). A retrospective analysis was conducted in Fudan University Shanghai Cancer Center. According to histological type, patients with benign PTBs were classified as a low-risk group, while borderline and malignant PTBs were classified as a high-risk group. The Cox regression model was adopted to identify factors affecting postoperative RFS in the two groups, and a nomogram was generated to predict recurrence-free survival at 1, 3, and 5 years. Among the 404 patients, 168 (41.6%) patients had benign PTB, 184 (45.5%) had borderline PTB, and 52 (12.9%) had malignant PTB. Fifty-five patients experienced postoperative local recurrence, including six benign cases, 26 borderline cases, and 22 malignant cases; the three histological types of PTB had local recurrence rates of 3.6%, 14.1%, and 42.3%, respectively. Stromal cell atypia was an independent prognostic factor for RFS in the low-risk group, while the surgical approach and tumor border were independent prognostic factors for RFS in the high-risk group, and patients receiving simple excision with an infiltrative tumor border had a higher recurrence rate. A nomogram developed based on clinicopathologic features and surgical approaches could predict recurrence-free survival at 1, 3, and 5 years. For high-risk patients, this predictive nomogram based on tumor border, tumor residue, mitotic activity, degree of stromal cell hyperplasia, and atypia can be applied for patient counseling and clinical management. The efficacy of adjuvant radiotherapy remains uncertain.

Radiotherapy with neoadjuvant chemotherapy versus concurrent chemoradiotherapy for ascending-type nasopharyngeal carcinoma: a retrospective comparison of toxicity and prognosis.

BACKGROUND: In the era of intensity-modulated radiotherapy (IMRT), the role of neoadjuvant chemotherapy (NACT) in treating ascending-type nasopharyngeal carcinoma (NPC) is under-evaluated. This study was to compare the efficacy of NACT followed by IMRT (NACT + RT) with the efficacy of concurrent chemoradiotherapy (CCRT) on ascending-type NPC. METHODS: Clinical data of 214 patients with ascending-type NPC treated with NACT + RT or CCRT between December 2009 and July 2011 were analyzed. Of the 214 patients, 98 were treated with NACT followed by IMRT, and 116 were treated with CCRT. The survival rates were assessed using Kaplan-Meier analysis, and the survival curves were compared using a log-rank test. RESULTS: The 4-year overall survival, locoregional failure-free survival, distant failure-free survival, and failure-free survival rates were not significantly different between the two groups (all P > 0.05). However, patients in the CCRT group exhibited more severe acute adverse events than did patients in the NACT + RT group during radiotherapy, including leukopenia (30.2% vs. 15.3%, P = 0.016), neutropenia (25.9% vs. 11.2%, P = 0.011), and mucositis (57.8% vs. 40.8%, P = 0.028). After radiotherapy, patients in the CCRT group exhibited significantly higher rates of xerostomia (21.6% vs. 10.2%, P = 0.041) and hearing loss (17.2% vs. 6.1%, P = 0.023). CONCLUSIONS: The treatment outcomes of the NACT + RT and CCRT groups were similar; however, CCRT led to higher rates of acute and late toxicities. NACT + RT may therefore be a better treatment strategy for ascending-type NPC.

The Chk1 inhibitor MK-8776 increases the radiosensitivity of human triple-negative breast cancer by inhibiting autophagy.

MK-8776 is a recently described inhibitor that is highly selective for checkpoint kinase 1 (Chk1), which can weaken the DNA repair capacity in cancer cells to achieve chemo-sensitization. A number of studies show that MK-8776 enhances the cytotoxicity of hydroxyurea and gemcitabine without increasing normal tissue toxicities. Thus far, there is no evidence that MK-8776 can be used as a radiotherapy sensitization agent. In this study, we investigated the effects of MK-8776 on the radiosensitivity of 3 human triple-negative breast cancer (TNBC) cell lines MDA-MB-231, BT-549 and CAL-51. MK-8776 dose-dependently inhibited the proliferation of MDA-MB-231, BT-549 and CAL-51 cells with IC50 values of 9.4, 17.6 and 2.1 µmol/L, respectively. Compared with irradiation-alone treatment, pretreatment with a low dose of MK-8776 (100-400 nmol/L) significantly increased irradiation-induced γH2A.X foci in the 3 TNBC cell lines, suggesting enhanced DNA damage by MK-8776, inhibited the cell proliferation and increased the radiosensitivity of the 3 TNBC cell lines. Similar results were obtained in MDA-MB-231 xenograft tumors in nude mice that received MK-8776 (15 or 40 mg/kg, ip) 26 d after irradiation. To explore the mechanisms underlying the radio-sensitization by MK-8776, we used TEM and found that irradiation significantly increased the numbers of autophagosomes in the 3 TNBC cell lines. Moreover, irradiation markedly elevated the levels of Atg5, and promoted the transformation of LC3-I to LC3-II in the cells. Pretreatment with the low dose of MK-8776 suppressed these effects. The above results suggest that MK-8776 increases human TNBC radiosensitivity by inhibiting irradiation-induced autophagy and that MK-8776 may be a potential agent in the radiosensitization of human TNBC.

Spirometric prediction equations and the relationship between metabolic syndrome and spirometric parameters from an island in Fujian, China.

BACKGROUND: We investigated risk factors for decreased lung function among Chinese island residents (≥30 years) to determine the relationship between metabolic syndrome (MS) and decreased lung function. METHODS: From October 17, 2011 to November 1, 2011, 2607 residents aged ≥30 years who lived on the Huangqi Peninsula of Fujian were enlisted by random cluster sampling. They completed a questionnaire designed according to the Burden of Obstructive Lung Disease (BOLD) questionnaire, and underwent physical examination, blood test, and lung function evaluation. We constructed spirometric prediction equations for forced vital capacity (FVC) and forced expiratory volume in one second (FEV1), determined the lower limits of normal for FVC, FEV1 and FEV1/FVC, and examined the relationship between lung function and MS. RESULTS: Prediction equations for normal island residents were as follows: FVC (L) = -0.023 × age (years) + 0.042 × height (cm) + 0.641 × weight (kg) - 3.607 (males); FVC (L) = -0.017 × age (years) + 0.030 × height (cm) + 0.009 × weight (kg) - 1.741 (females); FEV1 (L) = -0.023 × age (years) + 0.040 × height (cm) + 0.010 × weight (kg) - 2.999 (males); FEV1 (L) = -0.017 × age (years) + 0.026 × height (cm) + 0.007 × weight (kg) -1.135 (females). The odds ratio for MS for increased risk of decreased FVC was 4.623 (95%CI =3.626-5.894, P<0.001), and for increased risk of decreased FEV1 was 3.043 (95%CI =2.447-3.785, P<0.001). CONCLUSIONS: MS is a risk factor for decreased lung function in island residents ≥30 years old.

Trastuzumab improves locoregional control in HER2-positive breast cancer patients following adjuvant radiotherapy.

The benefit of adjuvant trastuzumab in disease-free and overall survival for human epidermal receptor 2-positive (HER2+) breast cancer patients is well established. However, the effect of trastuzumab on locoregional control remains unclear, particularly in patients treated with adjuvant radiotherapy (RT). In this study, we investigated the locoregional benefit of trastuzumab in patients with HER2+ breast cancer after adjuvant RT.Using a single institutional database, we identified 278 patients with stage II/III invasive HER2+ breast tumors receiving adjuvant RT between January 2008 and July 2011. We compared the locoregional outcomes of 134 patients who received trastuzumab to 144 patients without trastuzumab within the same period. Clinical and biological factors that might impact on the locoregional benefit of trastuzumab were also assessed.At the median follow-up of 45 months, trastuzumab significantly lowered the risk of locoregional recurrence (LRR) with a 3-year LRR rate of 2.4% versus 7.5% for the cohort with and without trastuzumab (P = 0.019). Trastuzumab was associated with a more significant locoregional benefit in the hormone receptor-positive (HR+)/HER2+ subgroup, with a 3-year LRR of 0% versus 6.7% in the cohort with and without trastuzumab (P = 0.027). For HR-/HER2+ breast tumor patients, the 3-year LRR rate was still lower for the cohort with trastuzumab (4.7% vs 8.6%). However, statistical significance was not found (P = 0.179). Both univariate and multivariate analyses confirmed that trastuzumab treatment was the only significant predictive factor for LRR (hazard ratio, 4.05; 95% confidence interval, 1.07-15.35; P = 0.039).Adjuvant trastuzumab in addition to RT is associated with significant reduced LRR risk in HER2+ breast cancer.

Therapeutic Effect of Carboxyamidotriazole on Adjuvant Arthritis in Rats.

OBJECTIVE: To study the effect of carboxyamidotriazole (CAI) on adjuvant arthritis (AA) in rats. METHODS: The rats were randomly divided into normal group,two vehicle groups (polyethylene glycol 400 control and normal sodium control group), CAI-treated groups (10, 20, and 40 mg/kg) and positive control dexamethasone group. Freund's completed adjuvant was used to induce AA in rats. The arthritis index (AI) was scored, and X-ray check of the hind limbs and histopathological examination were performed. The levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6 in the inflamed paw tissues were measured. RESULTS: The administration of CAI significantly decreased the AI, restored the body weights, and ameliorated the radiological and histopathological features of joint destruction in AA rats (P<0.05, P<0.01). In addition, CAI reduced the TNF-α, IL-1ß, and IL-6 levels in the inflamed paw tissues (P<0.05, P<0.01). CONCLUSION: CAI has therapeutic effect on AA rats, which may be achieved by decreasing the pro-inflammatory cytokines at the site of inflammation.

The efficacy of postoperative radiotherapy in localized primary soft tissue sarcoma treated with conservative surgery.

BACKGROUND: To evaluate the efficacy of postoperative radiotherapy (RT) on local failure-free survival (LFFS), distant metastasis-free survival (DMFS) and overall survival (OS) in patients with localized primary soft tissue sarcoma (STS) and to identify prognostic factors. METHODS AND MATERIALS: Between January 2000 and July 2010, 220 consecutive patients with localized primary STS, who received conservative surgery with or without postoperative RT, were enrolled in the study. Survival curves were constructed by the Kaplan-Meier method and log-rank test was used to assess statistical significance. Multivariate analysis was applied to identify the prognostic factors. RESULTS: After a median follow-up of 68 months (range, 5-127 months), the 5-year LFFS, DMFS and OS were 70.0, 78.2 and 71.2 %, respectively. Tumor size, histological subtypes, margin status and postoperative RT were independent predictors for OS. Postoperative RT was associated with a significant reduced local recurrence risk versus surgery alone (hazard ratio [HR] = 0.408, 95 % confidence interval [CI] 0.235-0.707, P = 0.001), with 5-year LFFS of 81.1 and 63.6 %, respectively (log-rank, P = 0.004). The log-rank test showed that postoperative RT had a tendency of improving OS compared with surgery alone, with 5-year OS of 74.8 and 65.0 %, respectively (P = 0.089). Multivariate analysis demonstrated that postoperative RT significantly reduced mortality rate compared with surgery alone (HR = 0.512, 95 % CI 0.296-0.886, p = 0.017), especially in patients with liposarcoma (p = 0.034). CONCLUSION: Postoperative radiotherapy reduce both local recurrence and STS mortality in patients with localized primary STS. The efficacy of RT on survival warrants further prospective study.

Predictors of Mastoiditis after Intensity-Modulated Radiotherapy in Nasopharyngeal Carcinoma: A Dose-Volume Analysis.

BACKGROUND: To identify predictors for development of mastoiditis after intensity-modulated radiation therapy (IMRT) in nasopharyngeal carcinoma (NPC). METHODS: Data for 146 NPC patients treated with IMRT was retrospectively reviewed under institutional ethics committee approval. Clinical factors associated with mastoiditis were analyzed. Dose-volume histogram analysis was performed for the Eustachian tube, tympanic cavity, mastoid air cells, cochlea, internal auditory canal and vestibular apparatus to relate doses to radiographic changes in the mastoid. Mastoiditis was assessed using magnetic resonance imaging and was classified as Grade 0 (none), 1 (mild), 2 (moderate) or 3 (severe); Grade 3 mastoiditis was the study end-point. RESULTS: Eighty-eight ears (36%) had radiation-induced mastoiditis: 38/244 (15.6%) mastoid complexes had Grade 1-2 mastoiditis and 50/244 (20.5%) mastoid complexes had Grade 3 mastoiditis. Multivariate analysis revealed a mastoid mean dose > 35.93 Gy (odds ratio [OR]=4.22, P=.003), Eustachian tube mean dose > 53.43 Gy (OR=2.16, P=.034) and advanced T category (T3 and T4; OR=10.33, P=.032) were negative prognostic factors for Grade 3 mastoiditis. CONCLUSIONS: Radiation-induced mastoiditis remains a common late toxicity in NPC after radiotherapy. The mean dose to the mastoid air cells and Eustachian tube should be limited to reduce the risk of radiation-induced mastoiditis.

Early Local Recurrence Presents Adverse Effect on Outcomes of Primary Breast Sarcoma: A Retrospective Study From Single Institute in China.

Primary breast sarcomas (PBSs) are spectrum heterogeneous sarcomas in breast and the optimal treatment for them is still under discussion. Our study was to investigate clinical characteristics and identify potential prognostic factors for this rare malignancy. The authors retrospectively reviewed 38 patients with PBSs between October 2000 and February 2014 in FuDan University Shanghai Cancer Center. Local control rate and overall survival (OS) were determined by Kaplan-Meier actuarial method. Univariate analysis and Cox proportional hazards model were applied to identify potential prognostic factors. With median follow-up of 40.19 months, 14 patients (14/38) were found with local recurrence. Extensive operation like mastectomy was not superior to local resection (P = 0.167). Three-year recurrence-free survival and OS rate were 61.9% and 89%, respectively. Larger tumor size and local recurrence were indicated as unfavorable prognostic factors in univariate analysis. Cox model identified narrow interval of recurrence free survival as an unfavorable factor (P = 0.048). Surgery remains crucial treatment for PBSs. Mastectomy, however, is not routinely necessary if clear margin could be achieved by local excision. Early recurrence indicates a poor OS.

Early cardiac toxicity following adjuvant radiotherapy of left-sided breast cancer with or without concurrent trastuzumab.

PURPOSE: To evaluate the influence of concurrent trastuzumab on the cardiotoxicity in patients receiving left-sided adjuvant radiotherapy. MATERIALS AND METHODS: Medical records of stage I-III left-sided breast cancer patients, including 64 receiving concurrent trastuzumab with radiotherapy and 73 receiving radiotherapy alone were retrospectively reviewed. All of the patients had normal LVEF after adjuvant chemotherapy. Information of doses volume to cardiac structures was collected. Cardiac events were assessed according to CTC 2.0. RESULTS: Median follow-up of LVEF and clinical assessment of cardiac function from the initiation of radiotherapy was 6.7 months (range 3-60.9) and 26 months (range 6.4-60.9), respectively. Grade 1 LVEF dysfunction occurred in 5 (7.8%) and 3 (4.1%) patients of the concurrent-trastuzumab and radiotherapy alone cohort, respectively. Trastuzumab was the only significant factor influencing absolute LVEF decrease in univariate analysis. In multivariate analysis of concurrent-trastuzumab cohort, IMC radiotherapy and start trastuzumab during radiotherapy were independent risk factors. For concurrent cohort, mean heart dose, as well as D10-D30, D50-D55, V5-V20 of the heart and D30-D45, D65-D75, V6-V15 of the LV were significantly higher in patients developing LVEF dysfunction. CONCLUSIONS: Concurrent trastuzumab and left-sided radiotherapy is well tolerated in terms of cardiotoxicity in patients with normal baseline cardiac function after adjuvant chemotherapy. However, increases in mean dose and low-dose volume of cardiac structures are associated with a higher risk of acute LVEF dysfunction.