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.

Multivariate analyses of locoregional recurrences and skin complications after postmastectomy radiotherapy using electrons or photons.

PURPOSE: We retrospectively analyzed factors of locoregional (LR) recurrence and skin complications in patients after postmastectomy radiotherapy (PMRT). METHODS AND MATERIALS: From January 1988 to December 1999, a total of 246 women with Stage II and III breast cancer received PMRT. Doses of 46 to 52.2 Gy/23 to 29 fractions were delivered to the chest wall (CW) and peripheral lymphatic drainage with 12 to 15 MeV single-portal electrons or 6MV photons. Of the patients, 84 patients received an additional 6 to 20 Gy boost to the surgical scar using 9 MeV electrons. We used the Cox regression model for multivariate analyses of CW, supraclavicular nodes (SCN), and LR recurrence. RESULTS: N3 stage (positive nodes >9) (p = 0.003) and diabetes (p = 0.004) were independent factors of CW recurrence. Analysis of ipsilateral SCN recurrence showed that N3 stage (p < 0.001) and electrons (p = 0.006) were independent factors. For LR recurrence, N3 (p < 0.001), T3 to T4 (p = 0.033) and electrons (p = 0.003) were significant factors. Analysis of skin telangiectasia revealed that electrons (p < 0.001) and surgical scar boost (p = 0.003) were independent factors. CONCLUSIONS: Photons are superior to single-portal electrons in patients receiving postmastectomy radiotherapy because of better locoregional control and less skin telangiectasia. In patients in whom the number of positive axillary nodes is >9, more aggressive treatment may be considered for better locoregional control.

Simultaneous integrated boost (SIB) of the parametrium and cervix in radiotherapy for uterine cervical carcinoma: a dosimetric study using a new alternative approach.

OBJECTIVE: To compare the dose distributions of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) using the simultaneous integrated boost (SIB) technique with that of the traditional midline block (MB) technique for boosting the parametrium in patients with cervical cancer. METHODS: Treatment plans using VMAT or IMRT with the SIB technique (VMAT-SIB and IMRT-SIB) and IMRT followed by the MB technique (IMRT-MB) were generated for each of the 10 patients with cervical cancer. For the SIB plans, 45-Gy and 50-Gy dose levels in 25 equal fractions were set for the pelvis planning target volume 45 (PTV45) and the parametrial boost volume (PTV50), respectively. For the IMRT-MB plans, the parametrium was sequentially boosted with the MB technique (5.4 Gy in three fractions) after pelvic IMRT (PTV45). RESULTS: Volume receiving 100% of the prescribed dose or more coverage of the PTV50 was significantly better for VMAT-SIB and IMRT-SIB than that for IMRT-MB (99.08 and 99.31% compared with 91.79%, respectively; p < 0.05). VMAT-SIB and IMRT-SIB both generated significantly greater doses to the organs at risk (OARs) except for the volume receiving 50 Gy or more doses, which were significantly lower for the bladder and bowel. Comparable results were achieved with VMAT-SIB and IMRT-SIB. CONCLUSION: The VMAT-SIB and IMRT-SIB techniques are promising in terms of dose distributions and tumour coverage, although these approaches might result in slightly higher doses of radiation to the OARs. Advances in knowledge: This is the first study to examine the feasibility of the SIB technique using IMRT or VMAT to boost the parametrium. The techniques dosimetrically produced better target coverage but resulted in slightly higher doses to the OARs.

Impact of treatment time-related factors on prognoses and radiation proctitis after definitive chemoradiotherapy for cervical cancer.

This study aimed to investigate the impact of treatment time-related factors on outcomes and radiation proctitis in patients undergoing concurrent chemoradiotherapy (CCRT) for cervical cancer. From September 2001 to December 2012, 146 patients with stage IIB cervical squamous cell carcinoma treated with CCRT were reviewed from a prospective cohort. Patients who received the same dose (45 Gy) of external beam radiation therapy (EBRT) were included in the analysis (n = 125). The same equivalent dose of 2 Gy (EQD2) of high-dose-rate intracavitary brachytherapy (HDR-ICBT) was delivered at either 4 fractions of 6 Gy or 6 fractions of 4.5 Gy. The effects of the overall treatment time (OTT) and interval between EBRT and HDR-ICBT on the cancer-specific survival (CSS), local recurrence (LR), and incidence of proctitis were compared. The treatment time-related factors did not adversely affect the CSS and LR rates. The multivariate analyses did not identify the OTT as an independent factor of CSS (P = 0.839) and LR (P = 0.856). However, OTT ≤56 days (P = 0.026) was identified as the only independent factor of overall proctitis. The 5-year Grade 2 or greater proctitis rates were 14.9% and 0% (P = 0.001) in patients with the EBRT to ICBT interval ≤5 days and >5 days, respectively. To reduce rectal damage without compromising prognosis, the gap between EBRT and HDR-ICBT should exceed 5 days in cervical cancer patients undergoing CCRT. Strictly limiting the OTT to 56 days may result in radiation proctitis without improvements in prognosis.

A prospective study to assess the bladder distension effects on dosimetry in intracavitary brachytherapy of cervical cancer via computed tomography-assisted techniques.

BACKGROUND AND PURPOSE: Intracavitary brachytherapy (ICBT) is as important as external beam radiotherapy (EBRT) for the radical radiotherapy of uterine cervical cancer. The degree of urinary bladder distension during ICBT may affect the dose distribution in the bladder and rectum, to which an overdose may increase the chance of developing treatment-related complications. The purpose of this prospective study was to assess and quantify the impact of bladder distension on dosimetry in ICBT in patients with cervical cancer. PATIENTS AND METHODS: We recruited 20 patients with cervical cancer during a 12-month period. Inclusion criteria included pathological diagnosis of cervical cancer with IA to IIIB stages, and intact uterus. Patients were evaluated for brachytherapy after EBRT, and eligible individuals (cervical os could be identified clearly) were invited enter to this protocol to receive ICBT. In the first brachytherapy, bladder preparation (evacuation and distension by a Foley catheter) and CT scan were performed soon after the insertion of CT-compatible applicators. Then the bladder wall doses [median dose, maximum dose and dose-volume histograms (DVH)] were calculated via the PLATO computer planning system (Nucletron PLATO-RTS version 2.0). The individual data regarding doses and DVH were collected and compared. Bladder distension may shift the applicator position, and posterior displacement of the applicator system may increase the dose to the rectal wall, so this effect was also evaluated. RESULTS: All the continuous variables of these 20 patients followed a normal distribution. By paired t-test and multiple linear regression analysis, we found that bladder distension statistically significantly decreased the median bladder wall dose with an average reduction of 48% of the dose of an empty bladder (P<0.001), and the maximum dose did not change; on the other hand, the bladder distension did not have any adverse effects on the rectal wall doses. CONCLUSIONS: Using CT-assisted three-dimensional techniques to assess the bladder and rectal wall doses is feasible. Bladder distension reduces the median dose in the bladder wall, which may reduce treatment-related complications.

Intensity-modulated radiotherapy as the boost or salvage treatment of nasopharyngeal carcinoma: the appropriate parameters in the inverse planning and the effect of patient's anatomic factors on the planning results.

The current study demonstrates that the large increase in normal tissue penalty often degrades target dose uniformity without a concomitant large improvement in normal tissue dose, especially in anatomically unfavorable patients. The excessively large normal tissue penalties do not improve treatment plans for patients having unfavorable geometry.

Postoperative radiotherapy in thymic carcinoma: treatment results and prognostic factors.

PURPOSE: To analyze the treatment results and prognostic factors of patients with primary thymic carcinoma treated by total or subtotal tumor resection followed by radiotherapy alone. METHODS AND MATERIALS: Between October 1987 and October 1997, 26 patients with thymic carcinoma were treated with complete or incomplete surgical resection and postoperative adjuvant irradiation without chemotherapy. The radiation was delivered with 10-MV X-ray given 5 days per week at 1.8 to 2 Gy per fraction. Total doses ranged from 40 to 70 Gy. All patients had at least 40 months of follow-up. RESULTS: The 5-year overall survival rate, local control rate, and distant metastasis-free rate were 77%, 91%, and 57%, respectively. Several prognostic factors, including sex, age, extent of resection (total resection vs. subtotal resection), Masaoka staging (early Stage I + II vs. advanced Stage III + IV), pathology (low-grade vs. high-grade), and postoperative radiation dose (> or =60 Gy vs. <60 Gy), were evaluated in univariate analysis. The Masaoka staging system was the only statistically significant predictor in overall survival rate (p = 0.0482) and distant metastasis-free rate (p = 0.0193). CONCLUSIONS: The Masaoka staging system is the most important prognostic factor in primary thymic carcinoma patients receiving postoperative radiotherapy alone. For resectable tumors, surgery and postoperative radiotherapy can achieve good local control, but the distant metastatic rate is still high. Further investigation of more effective chemotherapy is needed.

Clinical comparison of two linear-quadratic model-based isoeffect fractionation schemes of high-dose-rate intracavitary brachytherapy for cervical cancer.

PURPOSE: Two linear-quadratic model-based isoeffect fractionation schemes of high-dose-rate intracavitary brachytherapy (HDR-IC) were used to treat cervical cancer in two consecutive periods. Patient outcomes and complications were analyzed and compared. METHODS AND MATERIALS: Between November 1987 and December 1996, a total of 541 women diagnosed with cervical cancer were treated with curative-intent radiotherapy. Patients were categorized into two groups according to the two isoeffect schemes used. Group 1 consisted of 254 patients treated with external beam radiotherapy (EBRT) plus 7.2 Gy HDR-IC to Point A for three fractions in the first period. Group 2 consisted of 284 patients treated with EBRT plus 4.8 Gy HDR-IC for five fractions in the second period. The goal of the new scheme for the latter group was to deliver an isoeffect dose that maintained similar tumor control but reduced normal tissue complications. The calculated biologically effective dose (BED(10), assuming an alpha/beta ratio = 10) of EBRT plus HDR-IC for tumor and acute responding tissue in Groups 1 and 2 was 90 Gy(10) (52.8 + 37.2 Gy) and 88.6 Gy(10) (53.1 + 35.5 Gy), respectively. The corresponding BED(3) for late responding tissue (assuming an alpha/beta ratio = 3) in Groups 1 and 2 was 146.7 Gy(3) (73.3 + 73.4 Gy) and 134.4 Gy(3) (72 + 62.4 Gy), respectively. Patients were followed for 6.1-15.2 years (median, 9.8 years). RESULTS: Overall, 66 patients (12.2%) developed pelvic recurrence. Of these, 53 patients had central recurrence. Of the 53 patients with central recurrence, 24 (9.4%) were in Group 1 and 29 (10.1%) in Group 2 (p = 0.722). The actuarial pelvic control rate for Groups 1 and 2 was 88.2% and 86.3% at 5 years and 87.3% and 85.5% at 10 years, respectively (p = 0.504). The actuarial overall survival rate for Groups 1 and 2 was 63.5% and 56.1% at 5 years and 47.8% and 49.3% at 10 years, respectively (p = 0.734). The actuarial proctitis rate for Groups 1 and 2 was 49.7% and 32.7% at 5 years and 50.5% and 32.7% at 10 years, respectively (p <0.001). Most of the decrease in the rate of proctitis was a result of a decrease in the incidence of low-grade proctitis (38% vs. 22%). The incidence of high-grade complications remained unchanged, 8% vs. 7%. The actuarial cystitis rate for Groups 1 and 2 was 14.3% vs. 11.4% at 5 years and 24.1% vs. 15% at 10 years, respectively (p = 0.134). Multivariate analysis revealed that the fractionation scheme (three fractions vs. five fractions) was a significant factor influencing the proctitis rate (p = 0.004, hazard ratio = 0.807; 95% confidence interval, 0.697-0.934), but not the local pelvic control rate, overall survival rate, or cystitis rate. CONCLUSION: The treatment results of the two groups maintained similar outcomes, while the complications decreased. The linear-quadratic model correctly predicted this outcome. Biologically, the manipulation of the fraction size in our study suggested that the sensitivity of the late responding tissue to the fractional change from 7.2 Gy to 4.8 Gy in HDR-IC is high and detectable clinically. The success, however, had its limitations, and the improvement was confined to low-grade complications.

Health-related quality of life for nasopharyngeal carcinoma patients with cancer-free survival after treatment.

PURPOSE: To evaluate the health-related quality of life (HR-QOL) of nasopharyngeal cancer (NPC) patients with cancer-free survival after treatment and to investigate the factors correlated with their HR-QOL. METHODS AND MATERIALS: One hundred eighty-two NPC patients with cancer-free survival of more than 2 years after treatment were enrolled in the study. Data from the same number of people without a history of cancer, who had come to the hospital for health checkups, were also collected for comparison. The Chinese SF-36 questionnaire and nine items about head-and-neck functional impairments (HNFI) were self-reported by all participants at the clinics. Data relating to sociodemographic factors, cancer stage, and treatment of NPC survivors were analyzed. RESULTS: Psychometric tests revealed the excellent internal reliability (Cronbach's alpha: 0.87-0.96) and discriminative validity of the Chinese SF-36 used in Taiwan. Most functional domains of the Chinese SF-36 and all nine HNFI items were significantly worse in NPC survivors than in control subjects. No cancer or treatment-related variables significantly correlated with any functional domains of SF-36 or any items of HNFI for NPC survivors. Economic status, educational level, occupational status, and the number of comorbidities were the variables that significantly correlated with most functional domains of SF-36 for NPC survivors. Patients with more sufficient economic status, higher educational levels, with employment, or without comorbidity tended to enjoy better HR-QOL as detected by the SF-36. Salivation, hearing, and swallowing dysfunctions were the top three HNFI that disturbed NPC survivors. Economic status remained the most significant variable correlated with HNFI, including salivation, swallowing, neck stiffness, taste, and phonation. Survivors with better economic status reported less severe HNFI. CONCLUSIONS: NPC survivors had worse HR-QOL than healthy control subjects in the study. Socioeconomic status was the most significant variable that correlated with the HR-QOL of NPC survivors. This result might indicate that patients' superior individual characteristics and financial resources are important variables determining their ability to cope with cancer and treatment complications affecting their HR-QOL.

Treatment outcomes and prognostic factors of patients with supratentorial low-grade oligodendroglioma.

PURPOSE: Oligodendroglioma is a relatively rare central nervous system tumor. Currently, surgical intervention is the mainstay of treatment, and the role of postoperative radiotherapy (RT) remains a subject of controversy. The objective of this study was to investigate the prognostic factors, evaluate the treatment outcomes, and assess whether postoperative RT has a benefit on local control and overall survival rates. METHODS AND MATERIALS: This was a retrospective review of 52 consecutive adult patients with supratentorial low-grade oligodendrogliomas diagnosed at our institution between September 1980 and September 1998. Thirty-two received postoperative RT. Data were analyzed retrospectively to survey the significant prognostic factors for local control and overall survival. RESULTS: The 5-year overall and progression-free survival rate was 80% and 67%, respectively. Twenty-five patients experienced local disease progression during the follow-up period. In multivariate analysis, postoperative RT and age at diagnosis showed independent prognostic significance for overall survival. For progression-free survival, postoperative RT was the only independent prognostic factor. CONCLUSION: On the basis of the results of this study, we recommend considering postoperative RT as one of the standard adjuvant treatment modalities for patients with supratentorial low-grade oligodendroglioma, regardless of the extent of surgical resection. The optimal treatment strategy to maximize the treatment outcome should still be explored.

Intensity-modulated radiotherapy versus conventional three-dimensional conformal radiotherapy for boost or salvage treatment of nasopharyngeal carcinoma.

PURPOSE: To compare intensity-modulated radiotherapy (IMRT) and conventional three-dimensional conformal radiotherapy (3D-CRT) for the boost treatment of new-onset nasopharyngeal carcinoma (NPC) or the salvage treatment of locally recurrent NPC. METHODS AND MATERIALS: Between January 14 and February 23, 2000, 5-field 3D-CRT treatment plans were generated for 14 consecutive NPC patients using the ADAC Pinnacle planning system in Chang Gung Memorial Hospital, Kaohsiung, Taiwan. The planning data of these patients were later transferred to Memorial Sloan-Kettering Cancer Center, where new IMRT plans, also using 5-7 radiation fields were created for each patient using an inverse treatment planning system. The IMRT and 3D-CRT plans were compared for all 14 patients. The relationship between the anatomic shapes and locations of targets and the results of different plans were studied. RESULTS: Target doses were more homogeneous in IMRT plans. The average maximal brainstem dose (D(05), the dose received by 5% of the brainstem volume) decreased from 30.9% of the prescription dose with 3D-CRT to 15.3% and 14.7% with 5- and 7-field IMRT, respectively (p = 0.004 and 0.003, respectively, compared with 3D-CRT, paired Student's t test). Five anatomic factors were found that predicted greater benefits with IMRT. These factors were (1) vertical length of target >7 cm, (2) minimal distance between target and brainstem <0.1 cm, (3) maximal AP overlap of target and brainstem >0.6 cm, (4) maximal AP overlap of target and spinal cord >1 cm, and (5) vertical overlap of target and eyes >0 cm. For the 7 patients with at least 1 of these 5 anatomic factors, the benefits achieved by IMRT planning would have been greater than the benefits for the other 7 patients (p = 0.005, Fisher's exact test). CONCLUSION: For boost or salvage treatment of NPC, lower normal tissue doses and more homogeneous target doses were achieved with IMRT plans. For NPC patients with at least 1 of the 5 anatomic factors, IMRT is highly recommended.