Hypofractionated versus conventional fractionated postmastectomy radiotherapy for patients with high-risk breast cancer: a randomised, non-inferiority, open-label, phase 3 trial.

BACKGROUND: To our knowledge, no randomised study has compared postmastectomy hypofractionated radiotherapy with conventional fractionated radiotherapy in patients with breast cancer. This study aimed to determine whether a 3-week schedule of postmastectomy hypofractionated radiotherapy is as efficacious and safe as a 5-week schedule of conventional fractionated radiotherapy. METHODS: This randomised, non-inferiority, open-label, phase 3 study was done in a single academic hospital in China. Patients aged 18-75 years who had undergone mastectomy and had at least four positive axillary lymph nodes or primary tumour stage T3-4 disease were eligible to participate. Patients were randomly assigned (1:1) according to a computer-generated central randomisation schedule, without stratification, to receive chest wall and nodal irradiation at a dose of 50 Gy in 25 fractions over 5 weeks (conventional fractionated radiotherapy) or 43·5 Gy in 15 fractions over 3 weeks (hypofractionated radiotherapy). The modified intention-to-treat population (including all eligible patients who underwent randomisation but excluding those who were considered ineligible or withdrew consent after randomisation) was used in primary and safety analyses. The primary endpoint was 5-year locoregional recurrence, and a 5% margin was used to establish non-inferiority (equivalent to a hazard ratio <1·883). This trial is registered at ClinicalTrials.gov, number NCT00793962. FINDINGS: Between June 12, 2008, and June 16, 2016, 820 patients were enrolled and randomly assigned to the conventional fractionated radiotherapy group (n=414) or hypofractionated radiotherapy group (n=406). 409 participants in the conventional fractionated radiotherapy group and 401 participants in the hypofractionated radiotherapy group were included in the modified intention-to-treat analyses. At a median follow-up of 58·5 months (IQR 39·2-81·8), 60 (7%) patients had developed locoregional recurrence (31 patients in the hypofractionated radiotherapy group and 29 in the conventional fractionated radiotherapy group); the 5-year cumulative incidence of locoregional recurrence was 8·3% (90% CI 5·8-10·7) in the hypofractionated radiotherapy group and 8·1% (90% CI 5·4-10·6) in the conventional fractionated radiotherapy group (absolute difference 0·2%, 90% CI -3·0 to 2·6; hazard ratio 1·10, 90% CI 0·72 to 1·69; p<0·0001 for non-inferiority). There were no significant differences between the groups in acute and late toxicities, except that fewer patients in the hypofractionated radiotherapy group had grade 3 acute skin toxicity than in the conventional fractionated radiotherapy group (14 [3%] of 401 patients vs 32 [8%] of 409 patients; p<0·0001). INTERPRETATION: Postmastectomy hypofractionated radiotherapy was non-inferior to and had similar toxicities to conventional fractionated radiotherapy in patients with high-risk breast cancer. Hypofractionated radiotherapy could provide more convenient treatment and allow providers to treat more patients. FUNDING: National Key Projects of Research and Development of China; the Chinese Academy of Medical Science Innovation Fund for Medical Sciences; and Beijing Marathon of Hope, Cancer Foundation of China.

Patients with pathological stage N2 rectal cancer treated with early adjuvant chemotherapy have a lower treatment failure rate.

BACKGROUND: In this era of oxaliplatin-based adjuvant therapy, the optimal sequence in which chemoradiotherapy should be administered for pathological stage N2 rectal cancer is unknown. The aim of this study was to investigate this sequence. METHODS: In the primary adjuvant concurrent chemoradiotherapy (A-CRT) group (n = 71), postoperative concurrent chemoradiotherapy was administered before adjuvant chemotherapy. In the primary adjuvant chemotherapy (A-CT) group (n = 43), postoperative concurrent chemoradiotherapy was administered during or after adjuvant chemotherapy. Postoperative radiotherapy comprised 45-50.4 Gy in 25-28 fractions. Concurrent chemotherapy comprised two cycles of oral capecitabine (1,600 mg/m2) on days 1-14 and 22-35. Patients receiving adjuvant chemotherapy with four or more cycles of XELOX (oxaliplatin plus capecitabine) or eight or more cycles of FOLFOX (fluorouracil, leucovorin, and oxaliplatin) were included. RESULTS: Between June 2005 and December 2013, data for 114 qualified rectal cancer patients were analyzed. The percentages of patients in whom treatment failed in the A-CRT and A-CT groups were 33.8% and 16.3%, respectively (p = 0.042). More patients had distant metastases in the A-CRT group than in the A-CT group (32.4% vs. 14.3%, p = 0.028). Multivariate analysis indicated that the sequence in which chemoradiotherapy was administered (A-CT vs. A-CRT) was an independent prognostic factor for both estimated disease-free survival [hazard ratio (HR) 0.345, 95% confidence interval (CI) 0.137-0.868, p = 0.024] and estimated distant metastasis-free survival (HR 0.366, 95% CI 0.143-0.938, p = 0.036). CONCLUSIONS: In pathological stage N2 rectal cancer patients, administering adjuvant chemotherapy before chemoradiotherapy led to a lower rate of treatment failure, especially with respect to distant metastasis. Adjuvant chemotherapy prescribed as early as possible might benefit this cohort of patients in this era of oxaliplatin-based adjuvant therapy.

Survival benefit with IMRT following narrow-margin hepatectomy in patients with hepatocellular carcinoma close to major vessels.

BACKGROUND & AIMS: To investigate the role of post-operative intensity-modulated radiotherapy (IMRT) in patients receiving narrow-margin hepatectomy for hepatocellular carcinoma (HCC) located close to the major vessels. METHODS: This exploratory study involved 181 HCC patients. Of them, 116 were treated with narrow-margin (<1.0 cm) hepatectomy. Thirty-three of the 116 underwent postoperative IMRT (Group A), while 83 did not receive radiotherapy (Group B). The remaining 65 patients underwent wide-margin (≥1.0 cm) hepatectomy (Group C). Prognosis and patterns of recurrence were assessed in the three groups. RESULTS: The 3-year overall survival (OS) and disease-free survival (DFS) rates were 89.1 and 64.2% in Group A, 67.7 and 52.2% in Group B and 86.0 and 60.1% in Group C respectively. The OS and DFS of Group A and Group C patients surpassed those of Group B patients (Group A vs. B, P = 0.009 and P = 0.038; and Group C vs. B, P = 0.002 and P = 0.010). Patients in Groups A and C experienced significantly fewer early recurrences than did patients in Group B (P = 0.002). Furthermore, patients in Groups A and C experienced substantially fewer intrahepatic marginal (P = 0.048) and diffuse recurrences (P = 0.018) and extrahepatic metastases (P = 0.038) than did patients in Group B. No patient developed radiation-induced liver disease. CONCLUSIONS: Post-operative IMRT following narrow-margin hepatectomy may be a favourable therapy for both its safety profile and clinical benefit in patients with HCC located close to the major vessels.

Survival benefit with salvage radiotherapy for patients with locoregionally recurrent extranodal NK/T cell lymphoma, nasal type.

The purposes of this study are to evaluate prognosis in patients with locoregionally recurrent extranodal nasal-type NK/T cell lymphoma (NKTCL) and to determine the value of salvage radiotherapy. Forty-two patients with NKTCL who developed first locoregional recurrence with (n = 13) or without (n = 29) systemic failure were reviewed. Retreatment included chemotherapy (n = 20), radiotherapy (n = 13), and radiotherapy plus chemotherapy (n = 9). Fifteen patients were reirradiated for localized recurrent disease. The 5-year overall survival (OS) rate after recurrence was 40 %, with a median survival of 26 months. The 2-year OS rate and median OS were 68 % and 36 months for locoregional recurrence only, compared with 31 % and 14 months for both locoregional and systemic recurrence, respectively (p = 0.034). Subgroup analysis for patients with localized recurrent disease revealed an improved OS with radiotherapy. The 2-year and 5-year OS rates were 77 and 69 % for radiotherapy, respectively, compared with a 2-year OS rate of 50 % and median OS of 16 months for chemotherapy alone (p = 0.006). Patients with localized recurrence had a better prognosis than those with systemic recurrence. Salvage radiotherapy or reirradiation resulted in a favorable prognosis for patients with localized recurrent disease.

Favorable outcome with doxorubicin-based chemotherapy and radiotherapy for adult patients with early stage primary systemic anaplastic large-cell lymphoma.

The aim of this study was to analyze outcomes in adult patients with early stage systemic anaplastic large-cell lymphoma (ALCL) treated with doxorubicin-based chemotherapy and radiotherapy. Forty-six adult patients with early stage systemic ALCL received chemotherapy followed by radiotherapy. All patients except two received chemotherapy with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or a CHOP-like regimen. Twenty patients had stage I disease, and 26 patients had stage II disease. The 5-yr overall survival (OS), progression-free survival (PFS), and local control rates for all patients were 84.4%, 63.6%, and 90.8%, respectively. The 5-yr OS and PFS rates were 95.0% and 77.4% for Ann Arbor stage I disease, and 75.1% and 51.7% for stage II disease, respectively. Lymph node involvement was the main pattern of disease progression or relapse for these patients. Adult patients with early stage systemic ALCL treated with doxorubicin-based chemotherapy and radiotherapy had a favorable prognosis.

Clinical behavior and treatment outcome of primary nasal diffuse large B-cell lymphoma.

BACKGROUND: Nasal diffuse large B-cell lymphoma (DLBCL) is rare. The objective of this study was to evaluate the clinical features and treatment outcomes of patients with nasal DLBCL. METHODS: Twenty-five patients were included in the study. All patients received combination chemotherapy with or without radiotherapy. RESULTS: Patients with nasal DLBCL usually were older and were predominantly men with early stage disease, low frequency of B symptoms and elevated lactate dehydrogenase (LDH), good performance status, and a low-risk international prognostic index (IPI) score. The overall response rate after initial treatment was 76%, the 3-year overall survival (OS) rate for the whole group was 44%, and the median OS was 35 months. Performance status and IPI were significant prognostic factors for OS. For patients with IPI scores of 0 or 1, the 3-year OS rate was 54%, and the median OS was 52 months compared with 17% and 11 months, respectively, for patients with IPI scores of 2 or 3 (P = .033). The prognosis for patients who achieved a complete response (CR) was significantly better than that for patients who did not achieve a CR. Extranodal spread was the primary pattern of failure. CONCLUSIONS: The current results indicated that primary nasal DLBCL appears to have distinct clinical features; its poor outcome and propensity for extranodal failure illustrate the need for innovative therapies.

Failure patterns and clinical implications in early stage nasal natural killer/T-cell lymphoma treated with primary radiotherapy.

BACKGROUND: This study aimed to evaluate the failure patterns and clinical implications in patients with early stage nasal natural killer (NK)/T-cell lymphoma treated with primary radiotherapy. METHODS: Two-hundred fourteen patients were included. There were 182 cases of stage I and 32 cases of stage II disease. Patients received radiotherapy alone (n = 96) or radiotherapy and chemotherapy (n = 118). The median dose was 50 grays, and most patients received doxorubicin-based chemotherapy. RESULTS: The 5-year overall survival (OS) and progression-free survival rates for all patients were 72% and 65%, respectively. Sixty-three patients experienced treatment failure. The 5-year cumulative incidences of locoregional, systemic, and overall failures were 12.0%, 25.5%, and 32.9%, respectively. Stage and paranasal extension were significant predictors for systemic failure. The 5-year cumulative incidence of systemic failure was 22.6% for stage I disease versus 42.7% for stage II disease (P < .001), and 16.9% for limited disease versus 30.4% for paranasal extension (P < .001), respectively. Adding chemotherapy to extended involved-field radiotherapy did not significantly decrease the systemic failure rate nor improve survival. The cumulative incidence of systemic failure and OS rate at 5 years were 24.1% and 74.4% for combined modality therapy compared with 28.5% (P = 0.758) and 69.8% (P = 0.529) for radiotherapy alone. A very low incidence of cervical lymph node or central nervous system relapse was observed. CONCLUSIONS: Patients with early stage nasal NK/T-cell lymphoma have excellent locoregional control and favorable prognosis with radiotherapy, but patients with stage II disease or paranasal extension are at high risk of systemic failure, emphasizing the importance of integration of optimal radiotherapy with innovative systemic therapy.

Primary radiotherapy showed favorable outcome in treating extranodal nasal-type NK/T-cell lymphoma in children and adolescents.

Extranodal nasal-type natural killer (NK)/T-cell lymphoma is rarely observed in children and adolescents. We aim to investigate the clinical features, prognosis, and treatment outcomes in these patients. Thirty-seven patients were reviewed. There were 19, 14, 2, and 2 patients with stage I, stage II, stage III, and stage IV diseases, respectively. Among the patients with stage I and II disease, 19 patients received initial radiotherapy with or without chemotherapy, and 14 patients received chemotherapy followed by radiotherapy. The 4 patients with stage III and IV disease received primary chemotherapy and radiation of the primary tumor. Children and adolescents with extranodal nasal-type NK/T-cell lymphoma usually presented with early-stage disease, high frequency of B symptoms, good performance, low-risk age-adjusted international prognostic index, and chemoresistance. The complete response rate after initial radiotherapy was 73.7%, which was significantly higher than the response rate after initial chemotherapy (16.7%; P = .002). The 5-year overall survival (OS) and progression-free survival (PFS) rates for all the patients were 77.0% and 68.5%, respectively. The corresponding OS and PFS rates for patients with stage I and II disease were 77.6% and 72.3%, respectively. Children and adolescents with early-stage extranodal nasal-type NK/T-cell lymphoma treated with primary radiotherapy had a favorable prognosis.

Postoperative Chemoradiotherapy With Capecitabine and Oxaliplatin vs Capecitabine for Stage II to III Rectal Cancer: A Randomized Clinical Trial.

Importance: Several studies have explored the efficacy and toxic effects of concurrent 5-fluorouracil (5-FU)- or capecitabine-based chemoradiotherapy (CRT) with or without oxaliplatin in the neoadjuvant setting. Addition of oxaliplatin to 5-FU or capecitabine elicited similar outcomes but with significantly increased toxic effects; however, there is a need for randomized clinical trials comparing 2 CRT regimens for patients receiving CRT in the adjuvant setting. Objective: To explore the efficacy and toxic effects of oxaliplatin combined with postoperative concurrent capecitabine and radiotherapy (RT) for pathological stage II and III rectal cancer. Design, Setting, and Participants: This multicenter randomized clinical trial enrolled patients from 7 centers in China between April 1, 2008, and December 30, 2015. Patients with pathologically confirmed stage II and III rectal cancer were randomized (1:1) to receive concurrent CRT with capecitabine or capecitabine plus oxaliplatin. Analysis was conducted from December 31, 2019, to March 15, 2020. Interventions: RT comprised 45 to 50 Gy in 25 fractions of 1.8 to 2.0 Gy over 5 weeks. In the capecitabine with RT group, concurrent chemotherapy included 2 cycles of capecitabine (1600 mg/m2) on days 1 to 14 and 22 to 35. The capecitabine and oxaliplatin with RT group received identical postoperative RT to that in the capecitabine with RT group combined with capecitabine (1300 mg/m2) on days 1 to 14 and 22 to 35 and a 2-hour infusion of oxaliplatin (60 mg/m2) on weeks 1, 2, 4, and 5. Patients in both groups received adjuvant chemotherapy (capecitabine or fluorouracil and oxaliplatin) after CRT. Main Outcomes and Measures: The primary end point was 3-year disease-free survival (DFS). Results: A total of 589 patients (median [IQR] age, 55 [47-52] years; 375 [63.7%] men and 214 [36.3%] women) were enrolled, including 294 patients randomized to the capecitabine with RT group and 295 patients randomized to the capecitabine and oxaliplatin with RT group. Median (IQR) follow-up was 68 (45-96) months. Most patients had stage III disease (574 patients [75.9%]). Three-year DFS was 76.3% for the capecitabine with RT group and 74.1% for the capecitabine and oxaliplatin with RT group, and 5-year DFS was 72.0% for the capecitabine with RT group and 71.1% for the capecitabine and oxaliplatin with RT group (hazard ratio [HR], 1.07; 95% CI, 0.79-1.44; P = .68). There was no significant difference between groups in overall survival (HR, 0.93; 95% CI, 0.64-1.34; P = .70) or local recurrence (HR, 0.61; 95% CI, 0.31-1.22; P = .16). More grade 3 and 4 acute toxic effects were observed in the capecitabine and oxaliplatin with RT group than in the capecitabine with RT group (114 patients [38.6%] vs 84 patients [28.6%]; P = .01). Conclusions and Relevance: This randomized clinical trial found that addition of oxaliplatin to capecitabine-based postoperative CRT did not improve the efficacy of treatment but increased the risk of severe acute toxic effects. This finding highlights the basic role of postoperative capecitabine with RT for patients with locally advanced rectal cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT00714077.

Clinical features and treatment outcome of nasal-type NK/T-cell lymphoma of Waldeyer ring.

The clinical characteristics and prognosis remain unclear for nasal-type NK/T-cell lymphoma of Waldeyer ring (WR-NKTL). The aim of this study is to determine the clinical features and outcome. Ninety-one patients with WR-NKTL were reviewed. According to the Ann Arbor system, 15, 56, 12, and 8 patients had stage I, II, III, and IV. Of patients with stage I and II, 54 received combined chemotherapy and radiotherapy (CMT), 13 received radiotherapy alone, and 4 patients received chemotherapy alone. All 20 patients with stage III/IV received primary chemotherapy. The disease is characterized by predominance in young males, good performance, a propensity for nodal involvement, frequent stage II through IV diseases, low frequency of elevated LDH, low-risk international prognostic index (IPI), high sensitivity to radiotherapy, and intermediate sensitivity to chemotherapy. The 5-year overall survival and progression-free survival for all patients were 65% and 51%, respectively. The age, B symptoms, stage, and IPI were important prognostic factors. CMT tended to improve the survival compared with radiotherapy alone for patients with stage I and II diseases. Both nodal involvement and distant extranodal dissemination were the primary failure patterns. WR-NKTL appears to have distinct clinical characteristics and favorable outcomes.

Variable clinical presentations of nasal and Waldeyer ring natural killer/T-cell lymphoma.

PURPOSE: To determine the clinical characteristics, prognosis, and treatment outcome for patients with nasal natural killer (NK)/T-cell lymphoma (N-NKTL) and Waldeyer ring NK/T-cell lymphoma (WR-NKTL). EXPERIMENTAL DESIGN: A total of 145 patients with N-NKTL and 95 patients with WR-NKTL were compared. RESULTS: Compared with N-NKTL, WR-NKTL exhibited distinct differences in clinical features with a propensity for nodal involvement, more advanced stages, low elevated lactate dehydrogenase, intermediate chemosensitivity, and a favorable prognosis. Compared with patients with WR-NKTL, patients with N-NKTL were associated with a lower overall response (54% versus 89%) and higher persistent or progressive disease after initial chemotherapy (46% versus 11%; P = 0.000). The 5-year overall survival and progression-free survival rates were 67% and 56% for N-NKTL and 65% and 47% for WR-NKTL, respectively. Patients with stage II WR-NKTL showed favorable prognosis compared with those with stage II N-NKTL. Compared with radiotherapy alone, patients with early-stage WR-NKTL that received radiotherapy and chemotherapy showed a superior progression-free survival and improved overall survival. In contrast, the addition of chemotherapy to radiotherapy did not provide any survival benefit for patients with early-stage N-NKTL. CONCLUSIONS: N-NKTL and WR-NKTL represent heterogeneous groups with variable clinical features, responses, prognosis, and treatment options.

[Clinical features and prognostic factors of angioimmunoblastic T cell lymphoma].

OBJECTIVE: To retrospectively analyze the clinical features and prognostic factors of patients with angioimmunoblastic T-cell lymphoma (AITL). METHODS: The clinicopathological and follow-up data of 18 AITL patients undergoing integrated treatment from Feb. 1998 to April 2009 in our department were retrospectively analyzed. All of the patients received CHOP-like regimens as initial chemotherapy, including 4 once treated with radiotherapy and 1 with high dose therapy followed by autologous stem cell transplantation (HDT-ASCT) as upfront consolidation therapy. B-cell, T-cell and NK-cell subgroup proportions in the peripheral blood were tested by flow cytometry in 6 patients. RESULTS: The median age of the 18 patients was 55 years, male and female ratio was 2.6:1. Seventy-two percent of the patients were in an advanced stage. 72% of them had B symptoms, 69% hypergammaglobulinemia, 60% elevated LDH and 47% anemia. Forty-four percent achieved CR after initial treatment with CHOP-like regimens. With the median follow-up of 26 months, the overall 2-year survival and disease free survival (DFS) rates were 62.2% and 44.4%, respectively. In the univariate analysis, only age > 30 years and primary refractory disease adversely affected overall survival (OS); age > 30 years, advanced stage, B symptoms and splenomegaly adversely affected DFS. Four patients suffered from severe pneumonia during treatment, 2 of them died of respiratory failure. Flow cytometry of peripheral blood lymphocytes showed that 5 of the 6 tested cases had decreasing proportion of CD3(+)CD4(+) T cells, B cells and NK cells but elevated CD3(+)CD8(+) T cells. Two heavily treated patients achieved partial and complete response by thalidomide therapy, with a progression free survival (PFS) of 2 and 6+ months, respectively. CONCLUSION: AITL patients do not response well to CHOP-like regimens chemotherapy. Age < 30 years and sensitive to initial chemotherapy are associated with prolonged OS. Effectiveness of thalidomide in the treatment of AITL deserves further investigation. Peripheral blood lymphocytes test indicates that AITL patients suffered from both natural and acquired immune defects.

[Prognostic value of estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 in node positive breast cancer patients treated by mastectomy].

OBJECTIVE: To evaluate the prognostic value of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (Her-2) in node-positive breast cancer patients treated by mastectomy. METHODS: The clinicopathological data of 835 breast cancer patients treated by mastectomy from January 2000 to December 2004 were retrospectively analyzed. All had positive axillary nodes without distant metastases and with the immunohistochemistry staining of ER, PR and Her-2 available. 764 (91.5%) patients received anthracycline- and/or taxanes-based chemotherapy. 464 (55.6%) patients received hormonal therapy. Eight (1%) patients received trastuzumab. Postmastectomy radiotherapy were given to 352 out of 437(80.5%)patients with T3-T4 and/or N2-N3 disease and 68 out of 398(20.9%)patients with T1-2N1 disease. Patients were classified into 4 subgroups according to the status of hormone receptors (ER and PR, Rec) and Her-2: Rec(-)/Her-2(-) (triple negative), Rec(-)/Her-2(+), Rec(+)/Her-2(+) and Rec(+)/Her-2(-). End points were isolated locoregional recurrence (LRR), distant metastases (DM), disease-free survival (DFS) and overall survival (OS). RESULTS: 141 (16.9%) patients were Rec(-)/Her-2(-), 99 (11.9%) Rec(-)/Her-2(+), 157 (18.8%) Rec(+)/Her-2(+) and 438 (52.5%) Rec(+)/Her-2(-). Patients with Rec(+)/Her-2(-) breast cancer had a significantly lower 5-year LRR rate than others (6.2% vs. 12.9%, P = 0.004). Compared with patients with Rec(+) breast cancer, patients with Rec(-) breast cancer had significantly higher 5-year DM rate (26.4% vs. 19.7%, P = 0.0008), lower DFS rate (66.7% vs. 75.6%, P = 0.0001) and lower OS rate (71.4% vs. 84.2%, P = 0.0000). In multivariate analysis, Rec(+)/Her-2(-) was significantly associated with lower risk of LRR. Rec(-) was an independent prognostic factor for higher risk of DM, decreased DFS and OS. CONCLUSION: ER, PR and Her-2 are independent prognostic factors for locoregional recurrence and survival in node-positive breast cancer patients treated by mastectomy.

Radiation-Induced Lymphopenia Predicts Poorer Prognosis in Patients With Breast Cancer: A Post Hoc Analysis of a Randomized Controlled Trial of Postmastectomy Hypofractionated Radiation Therapy.

PURPOSE: The aim of this study was to determine whether radiation-induced lymphopenia affects the survival of patients with breast cancer. METHODS AND MATERIALS: Post hoc analysis was conducted on data from 598 patients with breast cancer from a randomized controlled trial comparing postmastectomy hypofractionated radiation therapy (HFRT; 43.5 Gy in 15 fractions over 3 weeks) with conventional fractionated radiation therapy (CFRT; 50 Gy in 25 fractions over 5 weeks). Mean peripheral lymphocyte count (PLC) at different time points in the 2 groups was compared by the t test. Disease-free survival and overall survival were analyzed by the Kaplan-Meier method and compared between groups by the log-rank test. RESULTS: Baseline PLC (pre-PLC) was comparable between HFRT and CFRT patients (1.60 ± 0.57 × 109/L vs 1.56 ± 0.52 × 109/L; P = .33). In both groups, the PLC declined steadily during the course of radiation therapy but started to recover at 1 month after radiation therapy. Incidence of lymphopenia was significantly lower in HFRT patients (45.4% vs 55.7%; P = .01). Nadir-PLC was significantly higher in HFRT patients (1.08 ± 0.37 × 109/L vs 0.97 ± 0.31× 109/L; P < .001), as was the nadir-PLC/pre-PLC ratio (0.72 ± 0.28 vs 0.67 ± 0.28; P = .02). Median follow-up was 57.6 months (interquartile range, 38.5-81.4). The 5-year disease-free survival was significantly lower in patients with a nadir-PLC/pre-PLC ratio <0.8 than in those with a ratio ≥0.8 (71.8% vs 82.6%; P = .01); however, overall survival was comparable between the groups (85.8% vs 90.6%; P = .24). CONCLUSIONS: The risk of radiation-induced lymphopenia in patients with breast cancer is lower with HFRT than with CFRT. A low nadir-PLC/pre-PLC ratio may predict poor prognosis.

Hypofractionated Versus Conventional Fractionated Radiotherapy After Breast-Conserving Surgery in the Modern Treatment Era: A Multicenter, Randomized Controlled Trial From China.

PURPOSE: No randomized trials have compared hypofractionated radiotherapy (HFRT) with conventional fractionated radiotherapy (CFRT) after breast-conserving surgery in the Asian population. This study aimed to determine whether a 3.5-week schedule of HFRT is noninferior to a standard 6-week schedule of CFRT in China. PATIENTS AND METHODS: Patients from 4 Chinese institutions who had undergone breast-conserving surgery and had T1-2N0-3 invasive breast cancers participated this study. Patients were randomly assigned (1:1) using a computer-generated central randomization schedule, without stratification, to receive whole-breast irradiation with or without nodal irradiation, followed by tumor-bed boost, either at a dose of 50 Gy in 25 fractions over 5 weeks with a boost of 10 Gy in five fractions over 1 week (CFRT) or 43.5 Gy in 15 fractions over 3 weeks with a boost of 8.7 Gy in three daily fractions (HFRT). The primary endpoint was 5-year local recurrence (LR), and a 5% margin of 5-year LR was used to establish noninferiority. RESULTS: Between August 2010 and November 2015, 734 patients were assigned to the HFRT (n = 368) or CFRT (n = 366) group. At a median follow-up of 73.5 months (interquartile range, 60.5-91.4 months), the 5-year cumulative incidence of LR was 1.2% in the HFRT group and 2.0% in the CFRT group (hazard ratio, 0.62; 95% CI, 0.20 to 1.88; P = .017 for noninferiority). There were no significant differences in acute and late toxicities, except that the HFRT group had less grade 2-3 acute skin toxicity than the CFRT group (P = .019). CONCLUSION: CFRT and HFRT with a tumor-bed boost may have similar low LR and toxicity.

[Postmastectomy radiotherapy in moderate-and high-risk elderly breast cancer patients].

OBJECTIVE: To analyze the role of postmastectomy radiotherapy (PMRT) in moderate- and high-risk elderly breast cancer patients. METHODS: The clinicopathological data of 874 breast cancer patients treated with mastectomy and axillary dissection were retrospectively analyzed. The T1-2N1 patients were defined as moderate- risk (IR) group, and T3-4 and/or N2-3 cases as high-risk (HR) group. The locoregional recurrence (LRR) and overall survival (OS) rates were calculated and compared according to different age groups and radiotherapy status. Kaplan-Meier method and Log-rank test was used for calculation and comparison of the survival curves of different patient groups. RESULTS: The median follow up time was 47 months. 108 (12.4%) patients were > or = 65 years. For patients who were < 65 and > or = 65 years, 18.1% and 15.3% received PMRT in the IR group, and 82.7% and 52.2% received PMRT in the HR group, respectively. For patients > or = 65 years, the 5-year LRR rates were 0% and 14.2% (P = 0.242) and 5-year OS rates were 100% and 75.2% (P = 0.159) for the PMRT-IR and non-PMRT-IR groups, respectively. The 5-year LRR rates were 0% and 14.1% (P = 0.061), 5-year OS rates were 84.6% and 77.4% (P = 0.597) for the PMRT-HR and non-PMRT-HR groups, respectively. For patients < 65 years, the 5-year LRR rates were 0% and 9.9% (P = 0.035) and 5-year OS rates were 87.0% and 82.1% (P = 0.739) for the PMRT-IR and non-PMRT-groups, respectively. The 5-year LRR rates were 7.2% and 26.1% (P = 0.000), 5-year OS rates were 79.2% and 57.7% (P = 0.000) for the PMRT-HR and non-PMRT-HR groups, respectively. CONCLUSION: With the increasing of age, there is a trend of decreasing use of postmastectomy radiotherapy in high-risk breast cancer patients. Postmastectomy radiotherapy can improve the locoregional control for high-risk patients and maybe considered even for those who are > or = 65 years.

[Long-term outcome of testicular seminoma in 294 patients].

OBJECTIVE: To analyze the correlation of long-term survival with the treatment strategies in patients with testicular seminoma. METHODS: Clinical data of 294 patients with testicular seminoma treated in our hospital between 1959 and 2004 were collected and analyzed. The median age of the patients was 37 years (range 13 - 70 years). Among them, 260 were in stage I disease, 16 in stage II, and 18 in stage III. The patients were treated by surgical resection plus chemotherapy and/or radiotherapy. The survival rate was calculated using Kaplan-Meier method and log-rank test using SPSS 13.0 software. RESULTS: The overall 5-, 10-, 20- and 30-year survival rates in this series were 92.1%, 91.8%, 85.5% and 71.4%, respectively. The major prognostic factor was found to be clinical stage. The patients with adjuvant chemotherapy after orchiectomy had better 10-year survival than the patients without (97.5% vs. 79.2%, P = 0.001). For stage II/III patients, the patients with chemotherapy and the patients with chemotherapy plus radiotherapy had a similar progression-free survival (PFS) and overall survival (OS) (P > 0.05). CONCLUSION: Testicular seminoma is sensitive to chemotherapy and radiotherapy, and a good cure rate can still be achieved in the relapsed patients with a salvage treatment. Therefore, wide excision and long-term chemotherapy should be avoided in order to maintain the quality of life in those patients.

[Radiosensitization of paclitaxel combined with radiation on nasopharygneal carcinoma cells (CNE-I) in vitro].

OBJECTIVE: To evaluate the radiosensitization of paclitaxel combined with radiation on nasopharygneal carcinoma cells( CNE-I) in vitro. METHODS: Human CNE-I cells were used for this study. Clonogenic assay was used to determine the drug dose of IC10, IC50 and IC90 for CNE-I Cells. The cells treated with different concentration of paclitaxel for 24 hours before or after radiation (dose ranged from 0 - 10 Gy ) were used to evaluate the radiosensitizing effect of paclitaxel combined with radiation. DNA flow cytometry was performed to define the cell cycle characteristics of cell populations treated for 0, 2, 6, 12, 18, 24 h with 0.1 nmol/L, 0.5 nmol/L, 1.0 nmol/L, 2.5 nmol/L paclitaxel, respectively. RESULTS: The dose of IC10, IC50 and IC90 for paclitaxel in CNE-I cells was 0.05 nmol/L, 1.0 nmol/L and 2.5 nmol/L, respectively. Paclitaxel treatment at concentration of 0.05 nmol/L and 1.0 nmol/L for 24 hours combined with X-ray irradiation before or after radiation showed radiosensitivity-enhansing effects in CNE-I cells. G2/M block was present when the drug concentrations were 2.5 nmol/L and 10.0 nmol/L, and it peaked at 18 hours. CONCLUSION: With an optimal paclitaxel/radiation combination, paclitaxel may exert a radiosensitizing effect on CNE-I cells. The effect might be related to the G2/M block caused by paclitaxel.

A phase I study of concurrent radiotherapy and capecitabine as adjuvant treatment for operable rectal cancer.

PURPOSE: To determine the maximum tolerated dose and the dose-limiting toxicity of capecitabine with standard radiotherapy (RT) as adjuvant treatment in patients with rectal cancer. METHODS AND MATERIALS: Patients with Stage II/III rectal cancer after surgery were eligible. Total RT dose was delivered as DT 50 Gy in fractions of 2.0 Gy/day for 5 weeks to the pelvic area. Capecitabine was administered concurrently with RT in escalating doses, twice daily with a 12-h interval, for two cycles of 14 days separated by a 7-day rest. Dose-limiting toxicity included Grade 3 or Grade 4 hematologic and nonhematologic toxicity. RESULTS: Twenty-four patients were enrolled at the following dose levels: 1,000 (3 patients), 1,200 (3 patients), 1,400 (3 patients), 1,500 (3 patients), 1,600 (6 patients), and 1,700 mg/m2/day (6 patients). Dose-limiting toxicity was observed in 1 patient at 1,600 mg/m2/day (Grade 3 diarrhea) and in 2 patients at 1,700 mg/m2/day (1 patient had Grade 3 and 1 Grade 4 diarrhea). CONCLUSION: The maximum tolerated dose (MTD) of capecitabine given concurrently with RT was 1,600 mg/m2, daily from the 1st to the 14th day, with a 7-day rest, for two cycles.

[Expression profile of nasal NK/T cell lymphoma by cDNA microarray].

OBJECTIVE: To investigate the changes of gene expression profile in nasal NK/T cell lymphoma. METHODS: Total RNA was extracted from the fresh nasal NK/T cell lymphoma tissue and normal lymph node. Fluorescent labeled cDNA was obtained through synthesizing process by reverse transcription. After hybridization in the two identical microarrays consisting of 4096 genes, overexpressed or underexpressed tumor related genes were analyzed. RESULTS: In both experimental group and control group, there were six samples. A total of 365 (8.9%) genes was found to be differentially expressed by a factor of twofold or greater in both of two identical cDNA microarrays, which included oncogenes, tumor supressor genes, cell cycle regulators, apoptotic and antiapoptotic factors, DNA transcription factors, DNA repair and recombination factors, signal transduction genes, protein translation genes, as well as a large number of metabolic genes. Thirty-seven of these genes were found to be differentially expressed by a factor of fourfold or greater. The biochemical functions of these differentially expressed genes were diverse. CONCLUSION: This study demonstrates that many different kinds of genes are possibly involved in the initiation and progression of nasal NK/T lymphoma. cDNA microarray technique is useful in screening cancer gene expression for nasal NK/T lymphoma.