Differences in the outcomes and complications between elderly and younger uterine cervical cancer patients treated by definitive radiotherapy - A propensity score-matched study.

PURPOSE: To evaluate the differences in the treatment outcomes and complications between elderly patients and younger patients with uterine cervical cancer (CxCa). METHODS AND MATERIALS: From April 1993 to December 2007, 138 CxCa patients aged ≥75years (Elderly group) and 334 CxCa patients aged <60years (Young group) who underwent definitive radiotherapy/chemoradiotherapy at our institution were reviewed. Two propensity score-matched cohorts of patients were selected from both age groups to evaluate the differences in the outcomes and complications. The overall survival (OS), cancer-specific survival (CSS), local failure (LF), distant failure (DF), late proctitis, and cystitis were compared between the age groups. RESULTS: The median follow-up time for survivors was 60.6months. A cohort of 99 pairs of patients was selected for the outcome comparison; there was a significant difference in the 5-year OS between the Elderly and Young groups (49.2% and 71.5%, respectively; p<0.001) but no differences in CSS, LF, and DF. Another cohort of 79 pairs of patients was selected for complication analysis. Significant differences between the Elderly and Young groups were observed in the 5-year cumulative grade 2 proctitis (39.7% and 17.2%, respectively; p=0.015) and grade 3 proctitis (18.1% and 6.2%, respectively; p=0.040). CONCLUSIONS: Although OS was worse in the elderly patients, no differences were observed in CSS, LF, and DF. Meanwhile, elderly patients tended to have higher radiation-related proctitis than younger patients. A more conservative treatment strategy for elderly CxCa patients is reasonable in our future practice.

The Therapeutic Benefit of Radical Resection for T4b Oral Cavity Squamous Cell Carcinoma with Partial or Complete Response After Radical Chemo-Intensity-Modulated Radiotherapy (IMRT).

BACKGROUND: This study investigated the therapeutic benefit of radical resection (SRR) for clinical T4b oral cavity squamous cell carcinoma (OSCC) with partial or complete response after radical chemoradiotherapy (CRT). METHODS: At the authors' institution, 79 patients with newly diagnosed non-metastatic T4b OSCC were treated with CRT from January 2009 to December 2014. All of them were irradiated using intensity-modulated radiotherapy (IMRT), with a radical dose (median 70 Gy; range 66-76 Gy) in the gross tumor area. Of the 65 cases achieving partial or complete response after CRT, 33 were treated further with SRR and 32 with adjuvant chemotherapy or observation. The locoregional control (LRC), overall survival (OS), and cancer-free survival (CFS) rates were compared between the two groups. RESULTS: The 3-year LRC, OS, and CFS rates were respectively 72.3, 75.1, and 72.6 % in the SRR group compared with 32.8, 47.7, and 44.3 % in the non-SRR group (p < 0.05). Multivariate analysis showed that SRR was the only statistically significant prognostic factor related to LRC, OS, and CFS. For those with SRR, pathologic downstaging was observed in 27 cases (81.8 %). Perioperative flap failure was observed in three cases (9.2 %) and neck wound necrosis in four cases (12.1 %). CONCLUSIONS: For T4b OSCC, incorporating SRR in the therapy is technically safe and has survival benefit, with a significant response after CRT applied by IMRT, with a radical dose in the gross tumor area.

Pretreatment Factors Associated with Recurrence for Patients with Cervical Cancer International Federation of Gynecology and Obstetrics Stage IB1 Disease.

BACKGROUND: Pretreatment prognostic information is lacking for patients with cervical cancer International Federation of Gynecology and Obstetrics (FIGO) stage IB1 disease. Thus, we attempted to identify a high-risk subgroup among them prior to treatment. METHODS: Cervical cancer FIGO stage IB1 patients who had received curative treatment with various modalities in our institute between January 2004 and December 2010 were enrolled. Pretreatment clinical parameters including age, squamous cell carcinoma antigen (SCC-Ag), carcinoembryonic antigen, hemoglobin (Hb) level, platelet count, histological type, and treatment modality were analyzed for treatment outcomes. RESULTS: One hundred ninety-seven patients were included with a median follow-up of 66 months (range 6-119 months). In Cox regression analysis, only SCC histology (HR 0.457, 95% CI 0.241-0.967, p = 0.017) was an independent factor predicting better disease-free survival (DFS). Among SCC histology, patients with an Hb level less than 12 g/dl and a SCC-Ag level more than 3 ng/ml had worse treatment outcomes. The 5-year DFS rates were 89.2, 69.3, and 44.4% for the patients at low-risk (SCC, Hb >12 g/dl, SCC-Ag ≤3 ng/ml), intermediate-risk (non-SCC), and high-risk (SCC, Hb ≤12 g/dl, SCC-Ag >3 ng/ml), respectively (p < 0.001). CONCLUSION: Non-SCC and SCC histology with both anemia and high pretreatment SCC-Ag level were associated with recurrence. Further validation studies are warranted for clarification.

Outcomes and Prognosis of Non-Elderly Patients with Brain Metastases-A Prospective Cohort Incorporating Individualized Assessment of Heart Rate Variability.

Outcomes and prognostic factors among patients with brain metastases (BM) have been widely studied, but seldom for the non-elderly. Heart rate variability (HRV) is a physiological phenomenon and has been shown as a survival prognostic factor in cancer patients. This study aimed to evaluate the outcomes and prognosis among non-elderly BM patients with the incorporation of HRV analysis. Forty non-elderly BM patients treated using whole brain radiotherapy (WBRT) were studied from January 2010 prospectively with 5-min electrocardiography (ECG) recordings. Individualized HRV was generated by the ECG, and the time domain HRV index SDNN was chosen for survival analysis. The median overall survival (OS) for the entire group was 6.21 months. Univariate analysis revealed that a KPS < 80 (p = 0.019) and an SDNN < 10 ms (p = 0.007) demonstrated statistical significance for OS; multivariate analysis confirmed that a KPS < 80 (p = 0.004; HR = 3.060, CI = 1.437-6.517) and an SDNN < 10 ms (p = 0.010; HR = 2.664, CI = 1.262-5.624) were independent prognostic factors. Prospective studies for risk stratification among non-elderly BM patients based on our results are warranted to validate our findings.

Developing a multivariable normal tissue complication probability model to predict late rectal bleeding following intensity-modulated radiation therapy.

Purpose: To develop a multivariable normal tissue complication probability (NTCP) model to predict moderate to severe late rectal bleeding following intensity-modulated radiation therapy (IMRT). Methods and materials: Sixty-eight patients with localized prostate cancer treated by IMRT from 2008 to 2011 were enrolled. The median follow-up time was 56 months. According to the criteria of D'Amico risk classifications, there were 9, 20 and 39 patients in low, intermediate and high-risk groups, respectively. Forty-two patients were combined with androgen deprivation therapy. Fifteen patients had suffered from grade 2 or more (grade 2+) late rectal bleeding. The numbers of predictors for a multivariable logistic regression NTCP model were determined by the least absolute shrinkage and selection operator (LASSO). Results: The most important predictors for late rectal bleeding ranked by LASSO were platelet count, risk group and the relative volume of rectum receiving at least 65 Gy (V65). The NTCP model of grade 2+ rectal bleeding was as follows: S = -17.49 + Platelets (1000/µL) * (-0.025) + Risk group * Corresponding coefficient (low-risk group = 0; intermediate-risk group = 19.07; high-risk group = 20.41) + V65 * 0.045. Conclusions: A LASSO-based multivariable NTCP model comprising three important predictors (platelet count, risk group and V65) was established to predict the incidence of grade 2+ late rectal bleeding after IMRT.

Analysis of prognostic factors and clinical outcomes in uterine cervical carcinoma with isolated para-aortic lymph node recurrence.

To evaluate clinical outcomes and to identify prognostic factors in isolated para-aortic lymph node (PALN) recurrence, we retrospectively reviewed 65 patients who developed PALN recurrence as the first site of tumor progression from a total of 1521 patients who were treated with curative pelvic radiation therapy (RT) for uterine cervical carcinoma between May 1993 and January 2017. Forty-five of the 65 patients received salvage therapy. The median salvage PALN radiation dose was 54 Gy (range: 18 to 62 Gy). Prognostic factors for overall survival (OS) and distant metastases (DMs) were analyzed with univariate and multivariate Cox regression. The median follow-up period for surviving patients was 61 months (4-202 months). The median OS was 27.7 months (0.3-202 months). The highest level of PALN metastases at or above the L1 spinal level (hazard ratio [HR] 9.88, 95% confidence interval [CI] 3.44-28.38, P<0.001) and the presence of leg edema and/or back pain at recurrence (HR 3.25, 95% CI 1.57-6.75, P=0.002) were significantly associated with worse OS. A significantly higher incidence of DMs (HR 5.97, 95% CI 2.05-17.35, P=0.001) was found in the patients with a high level (≥L1) of PALN metastases. Salvage RT (HR 0.35, 95% CI 0.17-0.71, P=0.004) and restaging with positron emission tomography/computed tomography (PET/CT) (HR 0.2, 95% CI 0.04-0.93, P=0.039) were independent predictors of a better OS. In conclusion, a high level (≥L1) of PALN metastases predicts poor survival and a high rate of DMs. Periodic surveillance for early detection and restaging by PET/CT imaging to identify the optimal treatment at recurrence is recommended.

Exacerbated radiodermatitis and bilateral subdural hemorrhage after whole brain irradiation combined with epidermal growth factor receptor tyrosine kinase inhibitors for brain metastases in lung cancer.

A 57-year-old male developed an adenocarcinoma lung cancer in November 2003. He received the full course chemotherapy but without a significant regression. The targeted therapy gefitinib was prescribed 2 years after diagnosis, producing a very good partial response. However, brain metastasis was diagnosed. A whole brain irradiation was performed for 37.5Gy with a fraction size of 2.5Gy and gefitinib was replaced with erlotinib on the 5th day after radiation therapy commenced for disease progressing. Unexpectedly, the patient developed a severe skin reaction in the region exposed to the radiation field, and a bilateral subdural hemorrhage, following radiation therapy. The reaction was thought to be triggered by the combination of radiation and epidermal growth factor receptor tyrosine kinase inhibitors, which may be responsible for hypersensitizing the radiation response in normal tissue in the unique individual.

Comparison of the outcome and morbidity for localized or locally advanced prostate cancer treated by high-dose-rate brachytherapy plus external beam radiotherapy (EBRT) versus EBRT alone.

OBJECTIVE: To compare the survival, gastrointestinal (GI) and genitourinary (GU) toxicity for localized or locally advanced prostate cancer treated by high-dose-rate-brachytherapy (HDR-BT) plus external beam radiotherapy (EBRT) versus EBRT alone at a single institute in Taiwan. METHODS: Eighty-eight patients with T1c-T3b prostate cancer consecutively treated by EBRT alone (33 patients) or HDR-BT+EBRT (55 patients) were studied. The median dose of EBRT was 70.2 Gy in the EBRT group and 50.4 Gy in the HDR-BT group. HDR-BT was performed 2-3 weeks before EBRT, with 12.6 Gy in three fractions over 24 h. RESULTS: Five patients (15.2%) in the EBRT group and seven (12.7%) in the HDR-BT group developed a biochemical relapse. The 5-year actuarial biochemical relapse-free survival rates were 65.0% in the EBRT group and 66.7% in the HDR-BT group (P = 0.76). The 5-year actuarial likelihood of late > or =Grade 2 and > or =Grade 3 GI toxicity in the EBRT versus HDR-BT group was 62.8 versus 7.7% (P < 0.001) and 19.6 versus 0% (P = 0.001), respectively. In a multivariate analysis, the only predictor for late GI toxicity was the mode of RT. The 5-year actuarial likelihood of late > or =Grade 2 and > or =Grade 3 GU toxicity in the EBRT versus HDR-BT group was 14.8 versus 15.9% (P = 0.86) and 3.6 versus 8.5% (P = 0.40), respectively. CONCLUSIONS: The addition of HDR-BT before EBRT with a reduced dose from the EBRT produces a comparable survival outcome and GU toxicity but a significantly less GI toxicity for prostate cancer patients.

Pretreatment prognostic factors of survival and late toxicities for patients with nasopharyngeal carcinoma treated by simultaneous integrated boost intensity-modulated radiotherapy.

BACKGROUND: To scrutinize the pretreatment prognosticators on survival and late toxicities in a homogenous cohort of nasopharyngeal carcinoma (NPC) patients treated by simultaneous integrated boost intensity-modulated radiation therapy (SIB-IMRT). METHODS: A total of 219 non-distant metastatic NPC patients consecutively treated by SIB-IMRT at a single institute were collected. The pretreatment factors including the socio-demographic variables, TNM stages, gross tumor volume (GTV), Epstein-Barr virus (EBV)-DNA, and hematologic inflammatory markers were analyzed. Cox model was used to screen the prognostic factors of late toxicities and four survival outcomes including locoregional relapse-free survival (LRRFS), distant metastasis-free survival (DMFS), failure-free survival (FFS), and overall survival (OS). RESULTS: Statistically significant inter-correlations were observed between the values of EBV-DNA, some hematologic inflammatory markers, GTV, and N classification. The 5-year LRRFS, DMFS, FFS, and OS rates were 87.9%, 89.4%, 79.4%, and 81.3%, respectively. Multivariate analysis revealed that advanced N classification (N2-3 vs. N0-1) remained the only significant negative prognosticator for all the four survival outcomes. An increased monocyte percentage and a decreased lymphocyte-to-monocyte ratio were significantly associated with poorer FFS and OS, respectively. Larger GTV was observed to be predictive of poorer LRRFS. Patients with T3-4 (HR: 3.5, 95% CI: 1.0-12.1, p = 0.048) or higher GTV (HR: 1.006, 95% CI: 1.001-1.011, p = 0.027) were associated with higher incidence of radiation neuropathy. CONCLUSION: N classification remains the most significant survival predictor for NPC patients treated by SIB-IMRT after adjusting these biomarkers. GTV impacts not only on locoregional control but also radiation neuropathy.

The different volume effects of small-bowel toxicity during pelvic irradiation between gynecologic patients with and without abdominal surgery: a prospective study with computed tomography-based dosimetry.

PURPOSE: To evaluate the effect of abdominal surgery on the volume effects of small-bowel toxicity during whole-pelvic irradiation in patients with gynecologic malignancies. METHODS AND MATERIALS: From May 2003 through November 2006, 80 gynecologic patients without (Group I) or with (Group II) prior abdominal surgery were analyzed. We used a computed tomography (CT) planning system to measure the small-bowel volume and dosimetry. We acquired the range of small-bowel volume in 10% (V10) to 100% (V100) of dose, at 10% intervals. The onset and grade of diarrhea during whole-pelvic irradiation were recorded as small-bowel toxicity up to 39.6 Gy in 22 fractions. RESULTS: The volume effect of Grade 2-3 diarrhea existed from V10 to V100 in Group I patients and from V60 to V100 in Group II patients on univariate analyses. The V40 of Group I and the V100 of Group II achieved most statistical significance. The mean V40 was 281 +/- 27 cm(3) and 489 +/- 34 cm(3) (p < 0.001) in Group I patients with Grade 0-1 and Grade 2-3 diarrhea, respectively. The corresponding mean V100 of Group II patients was 56 +/- 14 cm(3) and 132 +/- 19 cm(3) (p = 0.003). Multivariate analyses revealed that V40 (p = 0.001) and V100 (p = 0.027) were independent factors for the development of Grade 2-3 diarrhea in Groups I and II, respectively. CONCLUSIONS: Gynecologic patients without and with abdominal surgery have different volume effects on small-bowel toxicity during whole-pelvic irradiation. Low-dose volume can be used as a predictive index of Grade 2 or greater diarrhea in patients without abdominal surgery. Full-dose volume is more important than low-dose volume for Grade 2 or greater diarrhea in patients with abdominal surgery.