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Background: In clinical trials, adjuvant therapy (AT) has been shown to improve the prognosis in patients with gastric adenocarcinoma who undergo curative gastrectomy and adequate lymph node dissection. However, the optimal timing for initiating AT is still unclear. Method: We collected data from 538 patients with stage II-III gastric cancer who underwent curative gastrectomy and AT in two tertiary hospitals from 2006 to 2013. Patients were divided into the early group (≤8 weeks, n=393) and the late group (>8 weeks, n=145), based on the interval between gastrectomy and initiation of AT. Propensity score matching was applied according to baseline characteristics. Results: After 1:1 propensity score matching, an even distribution of characteristics in both groups (143:143) was achieved. The 5-year overall survival (OS) rates were 56.6% and 40.2% in the matched early and late groups, respectively (p=0.062), while the corresponding 5-year recurrence-free survival (RFS) rates were 57.6% and 46.4%, respectively (p=0.028). The time to AT initiation was correlated with RFS and had a positive association with OS. The 5-year distant metastasis-free survival was also significantly better (HR 0.682, 95% CI 0.472-0.985, p=0.040), suggesting an early AT results in a better outcome in patients. Conclusion: We observed that initiation of AT within 8 weeks of curative gastrectomy produces better disease control and may contribute to better overall survival.

It is probably safe to give delamanid beyond 6 months, with once-daily dosing after the first 1–2 months http://ow.ly/zoCv30jyCj0

We performed this study to analyze the survival of breast cancer patients with isolated supraclavicular lymph node metastasis (SLNM) and assess whether SLNM is distant metastasis or not. Sixty-three patients who developed an isolated SLNM among 3170 primary breast cancer patients between 1990 and 1999 were enrolled. The survival after SLNM was compared with that of 151 patients who developed local recurrences and 599 who had distant metastasis and was analyzed according to different levels and numbers of positive axillary nodes. Thirty-five of the 63 patients died during a median follow-up of 58.3 months. The 5-year overall survival (OS) rates after SLNM, local relapse, and distant metastasis were 33.6%, 34.9%, and 9.1%, respectively. The 5-year OS for patients with involved nodes confined to axillary level I was 74.4%, which was significantly better than that for involved nodes in level II or III or SLNM (49.2%, 52.8%, and 33.6%, respectively; P < .0001). For one to three positive axillary nodes, the 5-year OS was 83.2%, which was significantly better than that for four to nine positive nodes, more than nine positive nodes, and SLNM (62.6%, 42.3%, and 33.6%, respectively). There was no significant difference between SLNM and more than nine positive nodes. Surgical removal of the supraclavicular nodes was a significantly better prognostic factor for OS after SLNM (P = .0327). The 5-year OS after supraclavicular nodal metastosis, local relapse, and distant metastasis were 33.6%, 34.9%, and 9.1%, respectively. Good neck control either by surgery or chemotherapy achieved better survival.

Primary systemic therapy (PST) with a combination of epirubicin and paclitaxel achieves high response rates in locally advanced breast cancer (LABC), but considerable toxicity occurs and the patient's compliance is poor. In this open-label phase II trial toxicity of a weekly administration schedule was evaluated.On days 1 and 8 of each 3-week cycle, 45 patients with non-inflammatory breast cancer received epirubicin (35 mg/m(2), intravenous bolus) followed by paclitaxel (80 mg/m(2) in 500 ml of normal saline infused over 3 h) for 3 cycles. Surgery was done 2 weeks after primary chemotherapy, followed by another 6 cycles of adjuvant CEF (cyclophosphamide 500 mg/m(2), epirubicin 70 mg/m(2), 5-fluorouracil 500 mg/m(2)) chemotherapy.The median tumor size before and after PST was 6.0 and 2.0 cm, respectively. The clinical response rate was 96%, including 24% complete remission; 5 patients (11%) achieved pathologically complete response (pCR) including 3 patients with carcinoma in situ. Only 5 (11%) patients underwent breast conserving surgery although there were 15 patients suitable. Axillary nodes were negative in 16 (36%) of the 45 patients. Febrile neutropenia was found in 1 patient. There was no severe cardiac toxicity or serious adverse events.PST with weekly epirubicin and paclitaxel was an effective and well-tolerated combination for LABC, although only few patients underwent breast conserving surgery.

Background: The aim of the study was to evaluate the efficacy of contrast-enhanced magnetic resonance imaging (MRI) for preoperative assessment of palpable breast cancer after sonographically guided percutaneous core-needle biopsy. Methods: Thirty-six breast cancers in 35 women that had been diagnosed by sonographically guided core-needle biopsy prior to subsequent MRI were evaluated in this retrospective study. Radiological and pathological reports, multiplicity, retroareolar involvement, and the size of the breast cancers were reviewed. The cancer sizes, as derived from sonography and enhanced MRI, were correlated with histological size in greatest diameter by means of Pearson’s correlation. The threshold value for significance was set at P < .05. Results: Synchronous breast cancers were revealed in the index cases by means of enhanced MRI (10), sonography (8), and mammography (7). Two of the 36 index cancers (5.6%) benefited from MRI assessment. Retroareolar cancer extension was observed with enhanced MRI in five index cancers. Of these, one was also noted on both a sonogram and a mammogram. Four of the index cancers (11.1%) benefited from the enhanced MRI. Overall, five index cancers (13.9%) benefited from the enhanced MRI. With a gold standard of histology, the mean cancer sizes were underestimated by sonography and overestimated by enhanced MRI. In comparison with sonography, a stronger association was noted between MRI and histological measurements, with coefficients of 0.657 and 0.882, respectively (P < .001). Conclusions: In a clinical setting, MRI for preoperative assessment of breast cancers is warranted. Minimally invasive, percutaneous core-needle biopsy did not alter the clinical efficacy of the MRI evaluation.

There are two criteria for the diagnosis of Stage IIIB cervical cancer in the FIGO staging system: tumor fixation to the pelvic side wall and/or the presence of hydronephrosis due to tumor. However, we often encounter hydronephrosis without tumor fixed to the pelvic side wall or the level of ureteral obstruction not corresponding to the main tumor mass in the pelvis. The clinical implication of these phenomena remains unclear. We investigated the Stage IIIB population treated at the Mallinckrodt Institute of Radiology and hypothesized that, if hydronephrosis presents without tumor fixation to the pelvic side wall or if the level of ureteral obstruction is above the main pelvic tumor mass, it most likely resulted from external compression of ureter(s) by enlarged lymph nodes and, consequently, a worse outcome is expected.From 1959 to 1989, there were 297 patients with Stage IIIB cervical cancer who received definitive radiation therapy at the Mallinckrodt Institute of Radiology and were assessable for the presence of hydronephrosis and the level of ureteral obstruction. There were 281 patients who presented with tumor fixed to the pelvic side wall, and 62 of them were associated with concurrent hydronephrosis. An additional 16 patients presented with hydronephrosis without tumor fixation to the pelvic side wall. Among these 78 documented cases of hydronephrosis, the level of ureteral obstruction was above the true pelvis in 39 patients, and below the true pelvis in the other 39. Radiation therapy was individualized according to tumor extension and configuration; para-aortic lymph nodes were not routinely treated except in patients with clinical evidence of nodal metastasis.The progression-free survival (PFS) at 5 years was 35% in 62 patients with hydronephrosis and tumor fixed to the pelvic side wall vs. 43% in 213 patients with tumor fixed to the pelvic side wall only (p=0.12). However, PFS at 5 years decreased to 23% in 16 patients who presented with hydronephrosis without tumor fixation to the pelvic side wall (p0.001). When the level of ureteral obstruction was investigated, 5-year PFS was 39% vs. 22%, respectively, for the obstruction below vs. above the true pelvis (p=0.02). The majority of patients with ureteral obstruction above the true pelvis died of distant metastasis.The additional presence of hydronephrosis did not significantly worsen the PFS among Stage IIIB patients with tumor fixation to the pelvic side wall. However, hydronephrosis without tumor extending to the pelvic side wall or the level of ureteral obstruction above the true pelvis was associated with poor outcome due to a significant increase in distant failure. We propose that this population be separated from current Stage IIIB classification.

Radiation rhombencephalopathy and radiation myelopathy may occur in patients months or years after radiotherapy for malignancy of the head and neck.We obtained multimodal evoked potentials longitudinally in 26 patients with proven nasopharyngeal carcinoma. Recordings were made before radiotherapy and at 1 week, 3 months, 9 months, 15 months, and 24 months after radiotherapy. All absolute latencies of evoked response before and after radiation were within normal limits. However, the I-III interpeak latencies of brainstem auditory evoked potentials and the onset latencies of motor evoked potentials in the whole group of patients at 15 months after radiation were significantly longer than those before radiotherapy, whereas the latencies at 24 months were not significantly different. The N20 latencies of somatosensory evoked potentials after radiotherapy were significantly prolonged at 3 months of follow-up; the prolongation then became normal. They indicate that a subclinical reversible radiation-induced dysfunction may occur in the auditory, sensory, and motor systems.NEUROLOGY 1996;47: 521-525

Twenty-two patients, aged 16 to 67, who had malignant gliomas after surgical resection were treated with carmustine and cisplatin intravenous infusion before, during, and after radiotherapy. All patients had subtotal or total resection, or biopsy as the initial procedure. Twenty-one patients who had at least 2 cycles of chemotherapy and finished the whole course of radiotherapy were considered to be evaluable for responses. Among them, 5 had glioblastoma multiforme, 16 had anaplastic astrocytoma. The median time to tumor progression was 35 weeks (range 12-130 weeks) and median survival time was 66 weeks (range 10-156 weeks). Early progression occurred more frequently in patients with biopsy only and subtotal resection, and in patients with glioblastoma than in those with anaplastic astrocytoma. This combined modality treatment program was associated with reversible hematologic toxicity which was severe in 2 patients, and with ototoxicity in 1 patient, nephrotoxicity in 2 patients. Combination of carmustine and cisplatin with cranial irradiation for malignant gliomas is moderately toxic and appears to offer no obvious survival advantage compared with radiation therapy plus BCNU alone.

The role of pyrazinamide in the current treatment of multidrug-resistant (MDR) tuberculosis (TB) is uncertain. From a territory-wide registry of MDR-TB cases diagnosed between 1995 and 2009, we assembled a cohort of 194 patients with MDR pulmonary TB given fluoroquinolone-containing regimens. Stratified by pyrazinamide use and susceptibility, there were 83 users with pyrazinamide-susceptible MDR-TB (subgroup A), 24 users with pyrazinamide-resistant MDR-TB (subgroup B), 40 nonusers with pyrazinamide-susceptible MDR-TB (subgroup C), and 47 nonusers with pyrazinamide-resistant MDR-TB (subgroup D). We estimated the adjusted risk ratio (ARR) of early sputum culture conversion (ARR-culture) that occurred within 90 days posttreatment and that of cure or treatment completion (ARR-success) that occurred by 2 years posttreatment due to pyrazinamide use with susceptibility. In comparison with subgroup B, ARR-culture and ARR-success were 1.38 (95% confidence interval [CI], 0.89 to 2.12) and 1.38 (95% confidence interval [CI], 0.88 to 2.17), respectively. Corresponding findings were 0.99 (95% CI, 0.81 to 1.22) and 0.99 (95% CI, 0.78 to 1.26) in comparison with subgroup C and 1.09 (95% CI, 0.84 to 1.42) and 0.94 (95% CI, 0.74 to 1.20) in comparison with subgroup D. Early culture conversion significantly increased the incidence proportion of cure or treatment completion by 71% (95% CI, 26% to 133%). Selection bias among pyrazinamide nonusers might have underestimated the role of pyrazinamide. Comparison of pyrazinamide users showed that pyrazinamide increased the incidence proportion of early culture conversion and that of cure or treatment completion by a best estimate of 38% for both. This magnitude of change exceeded the 15 to 20% increase in the 2-month culture conversion rate of drug-susceptible TB that results from adding pyrazinamide to isoniazid and rifampin. Pyrazinamide is likely important in fluoroquinolone-based treatment of MDR-TB.

Multidrug-resistant (MDR)- tuberculosis (TB) and extensively drug resistant (XDR)-TB reportedly lead to increased household transmission. This is a retrospective cohort study of active TB occurring among household contacts exposed to MDR-TB. Of 704 contacts in 246 households, initial screening identified 12 (1.7%) TB cases (prevalent cases) and 17 (2.4%) contacts that subsequently developed active TB (secondary cases) after a median (range) duration of 17 (5–62.5) months. Eight prevalent cases and three secondary cases had MDR-TB. TB incidence rates per 100 000 person-years were 254.9 overall and 45.0 for MDR-TB. XDR-TB in the index MDR-TB patient significantly increased the odds of identifying a prevalent TB case to 4.8 (95% CI 1.02–22.5), and the hazard of finding a secondary TB case to 4.7 (95% CI 1.7–13.5). Molecular fingerprinting confirmed household transmission of MDR-TB. Of 20 retrievable isolates from 27 XDR-TB index cases, restriction fragment length polymorphism analysis showed clustering among 13 (65%), with 11 (55%) due to recent transmission by n-1 method and an identifiable household source in only three (27.2%) of the 11 cases. XDR-TB relative to MDR-TB significantly increases household transmission of TB, probably reflecting prolonged/higher infectivity, and indicating a need for prolonged household surveillance. XDR-TB may largely transmit outside of the household settings.

Background: To evaluate pathological complete response rate and to identify the predictor of response after primary systemic chemotherapy (PST) with weekly docetaxel and epirubicin for locally advanced breast cancer. Methods: Sixty-three patients with locally advanced breast cancer received three cycles PST on day 1 and 8 of each 3-week cycle with epirubicin and docetaxel (epirubicin 45 mg/m 2 intravenous bolus, docetaxel 35 mg/m 2 in 100 ml normal saline infused 1 h), followed by surgery and adjuvant chemotherapy with cyclophosphamide, epirubicin and 5-fluorouracil. The pathological complete response was defined as no invasive carcinoma in breast and axillary nodes after PST. Results: The median tumor sizes (by ultrasound) before and after PST were 6.2 and 2.5 cm, respectively. The negative estrogen receptor (ER) by immunochemical stain was found in 33 (52.4%) patients and HER-2/neu-overexperssion in 12 (19.0%) patients. Clinical overall response rate (ORR) was 89% (95% confidence intervals (95% CI: 81‐97), including 38% complete response (95% CI: 26‐50), sonographical ORR was 97% (95% CI: 93‐100). The pathological complete response were found in 11 patients (18%, 95% CI: 9‐27), and 15(24%, 95% CI: 13‐35) patients achieved breast only pathological complete response. Nine (27.3%) of thirty-three ER (2) patients and 5 (41.7%) of 12 HER2-positive patients achieved pathological complete response. Conclusion: PST with weekly docetaxel and epirubicin were well-tolerated and very high pathological complete response rate was achieved in HER-2/neu -overexpression tumors.

Between 1979 and 1985, 561 patients with nasopharyngeal carcinoma were reviewed to determine prognostic factors that may influence survival. Sex (p = 0.294) and histopathology (p = 0.677) had no correlation to the actuarial survival, whereas the site of cervical metastasis (p = 0.001) and the radiation doses to the nasopharynx and regional lymph nodes (p = 0.03) were both significant when one used univariate analyses. Cox's multivariate regression model revealed that the presence rather than the site of distant metastases was the single most important independent factor influencing the treatment outcome (p less than 0.0001). The addition of chemotherapy, on the other hand, did not show a survival benefit even when one took available confounding factors into account. There are, however, survival advantages associated with: (a) young age (less than or equal to 40 years), (b) asymptomatic status, (c) Stage I or II lesions, and (d) biopsy via nasopharynx instead of neck nodes. These favorable prognostic factors may be used for therapeutic guidance and end-result reporting.

Background. Lhermitte's sign (LS) is a side effect of radiotherapy (RT) on the spinal cord and typically occurs shortly after the procedure has been conducted. When treating patients with cancer of the head and neck region with irradiation, it remains difficult to avoid exposing the cervical spinal cord to unintended radiation. In this study, we focused on nasopharyngeal cancer (NPC) alone and looked for various parameters that might influence the occurrence of LS associated with this disease after RT. Methods. From 1979 through 1990, 1171 patients with NPC completed RT either with or without chemotherapy at the Lin-Kou Medical Center, Chang Gung Memorial Hospital (CGMH), Tao-Yuan, Taiwan; the RT regimens for these treated patients were very similar. The nasopharyngeal tumor was treated to 75 Gy by photon teletherapy and after-loading brachytherapy. The neck lymphatics were irradiated with photon irradiation to 46.8 Gy and then boosted with electron beams to 10 to 30 Gy, in accordance with the patient's nodal status, either unilaterally or bilaterally. Every patient was followed monthly for the first 3 months after therapy and subsequently every 2 to 3 months for the next 2 years and, finally, every 6 months thereafter. At follow-up, a neurologic checkup of each patient was performed to determine whether any injury to the spinal cord or brain stem had arisen. Results. LS was observed for 121 patients (10.3%). The median development time for such signs was 3.0 months after the completion of RT (range, 0.2–72 months), and the appearance of such a sign lasted 1 to 82 weeks (median, 17 weeks). No statistically significant differences between the sexes were noted in the development of such a sign (p = .5263),or among various T classifications (p = .0757) and N classifications (p = .4412). The incidence of LS was significantly lower for those patients who had also received chemotherapy than it was for those who had not (p = .003), and it was also lower for patients older than 60 years than for those younger than 60 years (p = .0061). Of the subjects who did not undergo neck-lymphatic boosting or who had undergone only unilateral neck-lymphatic boosting, 7.2% had LS develop, whereas 11.5% of patients who had been boosted bilaterally had LS develop (p = .0285). Conclusions. The incidence of LS associated with NPC and after RT was higher in patients who underwent bilateral neck-lymphatic boosting by electron beams than for those who underwent unilateral boosting or who did not undergo boosting. A correlation between increased incidence of LS and RT dose on the cervical spinal cord was noted when the cord dose exceeded 48.9 Gy. Therefore, wherever possible, a CT simulator and a three-dimensional treatment-planning system should necessarily be used to verify the dose distribution of electron-beam RT to diminish the chance of radiation overdose on the cervical cord. © 2004 Wiley Periodicals, Inc. Head Neck27: 187–194, 2005

The aim of this study was to examine the impact of radiation treatment on olfactory function in patients with nasopharyngeal carcinoma (NPC). An olfactory function test battery was administered to 25 adult NPC patients having received radiotherapy, 24 adult nasopharyngeal carcinoma patients awaiting to receive radiation treatment, and 36 adult normal control subjects. Members of the three groups were matched in terms of age, educational level, and full-scaled IQ score. Comparing the test results revealed that the NPC patients with radiotherapy had olfactory information processing impairments including absolute threshold, odour-tactile cross-modality matching, verbal identification of odours, and recall and recognition of identity of odours. The deficits of suprathreshold olfactory functioning in these patients did not seem to arise from impaired absolute threshold sensitivity. Provided that the results are reproducible, an evaluation of olfactory functioning in NPC patients during the period of radiotherapy may be useful for detecting or even avoiding side effects of radiation.

OBJECTIVE To evaluate radiotherapy dose and length of treatment in the control of early stage nasopharyngeal carcinoma (NPC) treated with a combination of external radiotherapy and brachytherapy, MATERIALS & METHODS We reviewed the records of 133 patients with early stage nasopharyngeal carcinoma (stage I or II, AJC/UICC staging system) who received definitive radiotherapy in Chang Gung Memorial Hospital from 1979 to 1991. The median follow-up time was 7.1 years with a minimum of 2 years. All patients were treated with megavoltage external radiotherapy to the nasopharynx area (63-72 Gy) followed by high dose rate intracavitary brachytherapy (5-16.5 Gy in one to three fractions, spaced 1-2 weeks apart). The median total dose and time of irradiation was 75 Gy (69.8-81.4 Gy) and 11.6 weeks (7.8-20 weeks) respectively. Survival analysis was used to examine the effect of several variables on prognosis. RESULTS The 5-year rates were 86.4% for local control, 84.7% for disease free survival, 88.5% for actuarial survival and 84.2% for overall survival. The treatment group (combination of time and dose of irradiation) was the most important prognostic factor according to Cox's proportional hazard model. Patients receiving radiation at a total dose of < or = 75 Gy completed in < 12 weeks showed the best prognosis. CONCLUSION Treatment time and total treatment dose are both important factors in treating early stage NPC. Decreasing the total radiation time to < 12 weeks and not exceeding a radiation dose of 75 Gy gave the best results.

Purpose : A multivariate analysis of prognostic factors of treatment outcome of pineal tumor. Methods and Materials : From February 1979 to June 1987, 25 patients with primary pineal tumors were treated in our department. Patients were treated with either AECL Co-60 unit or 10 MV linear accelerator to the primary tumor with an adequate margin or to the whole brain (median dose of 36 Gy) with or without a cone-down boost of 10 to 20 Gy. Craniospinal irradiation was performed in two patients with positive CSF cytology. Minimum follow-up was 40 months. Patients were further stratified according to tumor type. Group I consisted of seven patients with pineal germinoma. Group II included nine patients with nongerminoma, and Group III represented nine patients treated without a histological verification but clinical diagnosis. Results : The relapse-free survival (RFS) of Group I patients was 100% and 86% at 2 and 5 years, respectively. Relapse-free survival was 55% and 21% at 2 and 5 years, respectively, for Group II patients. Six of 9 patients in Group II died of disease due to either local recurrence or tumor seeding. Eight of 9 patients in Group III remain no evidence of disease, and RFS was 89% at 2 and 5 years. Multivariate analysis revealed that tumor histology is the only significant prognosticator. Age, gender, type of surgical procedure, RT field, and tumor dose were not. Cox's regression model also failed to demonstrate a significant correlation of tumor seeding with the type of surgery. Conclusion : The type of tumors in the pineal region dictates the treatment outcome. Definitive radiation therapy is effective in controlling germinoma, whereas a more aggressive approach is needed to improve local control for nongerminoma. For a localized pineal lesion, we advocate that treatment can be tailored to the primary tumor with adequate margins. However, for locally advanced tumors whole brain or craniospinal irradiation should be considered. No definitive correlation between type of surgery and the probability of tumor seeding was identified.

The results of radiation treatment of nasopharyngeal carcinoma (NPC) have recently been improved, but the prognosis remains relatively poor in cases with cranial nerve (CN) involvement. A total of 109 cases with histologically-proven NPC and cranial nerve involvement treated during 1979-1985 were reviewed and analysed. Definitive radiotherapy (RT) was given to patients with a high upper margin of the RT field at 2.5 cm above the base of the skull to a total dose of 70.2 Gy/39 fractions/8 weeks, with two applications of intranasopharyngeal brachytherapy. There were 37 cases (34%) in Group I (upward invasion only) and 72 cases (66%) in Group II (bidirectional invasion). Abducens, trigeminal, oculomotor and facial were the commonly involved nerves. Headache was the major symptom at diagnosis and was present in 82.6% of the patients, significantly higher than in general NPC cases (p less than 0.005). Fifty per cent (31/62) achieved complete response to definitive RT, but it did not correlate well with survival rate. The residual neurological deficit of each CN ranged from 31 to 57%. The actuarial 5-year survival rates of Groups I and II were similar in spite of neck lymph node metastasis in Group II (33% (I) compared with 24% (II); p greater than 0.05). Cases with single CN deficit did not show better results than those with multiple CN involvements. Five-year survivors were seen only in those who received a complete course of definitive RT.