To compare the benefit achieved by concurrent chemoradiotherapy (CRT) and/or accelerated fractionation (AF) vs. radiotherapy (RT) alone with conventional fractionation (CF) for patients with ...T3-4N0-1M0 nasopharyngeal carcinoma (NPC).
All patients were irradiated with the same RT technique to > or =66 Gy at 2 Gy per fraction, conventional five fractions/week in the CF and CF+C (chemotherapy) arms, and accelerated six fractions/week in the AF and AF+C arms. The CF+C and AF+C patients were given the Intergroup 0099 regimen (concurrent cisplatin plus adjuvant cisplatin and 5-fluorouracil).
Between 1999 and April 2004, 189 patients were randomly assigned; the trial was terminated early because of slow accrual. The median follow-up was 2.9 years. When compared with the CF arm, significant improvement in failure-free survival (FFS) was achieved by the AF+C arm (94% vs. 70% at 3 years, p = 0.008), but both the AF arm and the CF+C arm were insignificant (p > or = 0.38). Multivariate analyses showed that CRT was a significant factor: hazard ratio (HR) = 0.52 (0.28-0.97), AF per se was insignificant: HR = 0.68 (0.37-1.25); the interaction of CRT by AF was strongly significant (p = 0.006). Both CRT arms had significant increase in acute toxicities (p < 0.005), and the AF+C arm also incurred borderline increase in late toxicities (34% vs. 14% at 3 years, p = 0.05).
Preliminary results suggest that concurrent chemoradiotherapy with accelerated fractionation could significantly improve tumor control when compared with conventional RT alone; further confirmation of therapeutic ratio is warranted.
Purpose:
In this article, the breath-hold and gating concepts were combined for application of lung cancer radiation treatment. The tumor movement was immobilized based on deep inspiration breath ...hold (DIBH), in which the breath-hold consistency and stability were monitored by infrared (IR) tracking and controlled by gating with a predefined threshold. The authors’ goal is to derive the benefits from both techniques, namely, the minimized treatment margin and the known advantages of deep inspiration. The efficacy of the technique in terms of tumor immobility and treatment setup accuracy was evaluated in the study.
Methods:
Fourteen patients who were diagnosed with non small cell lung cancer were included in this study. The control of tumor immobility was investigated interfractionally and intrafractionally. The intrabreath-hold tumor motion was devised based on the external marker movement, in which the tumor-marker correlation was studied. The margin of the planning target volume (PTV) was evaluated based on two factors: (1) The treatment setup error accounts for the patient setup and interbreath-hold variations and (2) the intrabreath-hold tumor motion in which the residual tumor motion during irradiation was studied.
Results:
As the result of the study, the group systematic error and group random error of treatment setup measured at the isocenter were
0.2
(
R
)
±
1.6
,
1.0
(
A
)
±
2.0
, and
0.3
(
S
)
±
1.5
mm
in the left-right (LR), anterior-posterior (AP), and caudal-cranial (CC) directions, respectively. The Pearson correlation coefficient were 0.81 (LR), 0.76 (AP), and 0.85 (CC) mm and suggest tendency in linear correlation of tumor and marker movement. The intrabreath-hold tumor was small in all directions. The group PTV margins of 3.8 (LR), 4.6 (AP), and 4.8 (CC) mm were evaluated to account for both setup errors and residual tumor motion during irradiation.
Conclusions:
The study applies the DIBH technique in conjunction with IR positional tracking for tumor immobilization and treatment setup localization. The technique not only proved to be reliable in terms of good tumor immobility and accurate treatment positioning but also to be potentially useful for dose escalation treatment as regarding of the substantially reduced PTV margin and minimizing radiation toxicity from the fully expanded lung volume.
To investigate any possible therapeutic gain from dose escalation with brachytherapy for early T stage nasopharyngeal carcinoma (NPC).
One hundred forty-five patients with T1-2b N0-3 NPC were boosted ...with high-dose-rate intracavitary brachytherapy after completion of two-dimensional external radiotherapy (ERT) during the period from 1999 to 2003. To compare the efficacy of brachytherapy boost, another 142 patients with T1-2b N0-3 disease who were treated with ERT alone during 1994 to 1999 were evaluated. All patients were treated with ERT to a total dose of 66 Gy in 6.5 weeks. The brachytherapy boost group was given 10-12 Gy in 2 weekly fractions.
Dose escalation beyond 66 Gy with brachytherapy boost was shown to improve local control and survival. The 5-year actuarial local failure-free survival, regional failure-free survival, distant metastasis-free survival, progression-free survival, cancer-specific survival, and overall survival rates for the brachytherapy group and the control group were 95.8% and 88.3% (p = 0.020), 96% and 94.6% (p = 0.40), 95% and 83.2% (p = 0.0045), 89.2% and 74.8% (p = 0.0021), 94.5% and 83.4% (p = 0.0058), and 91.1% and 79.6% (p = 0.0062), respectively. The 5-year major-complication-free survival rate was 89.5% for the brachytherapy group and 85.6% for the control group (p = 0.23).
For patients who are treated with two-dimensional treatment techniques, dose escalation with brachytherapy boost improves local control and overall survival of patients with T1-T2a and possibly non-bulky T2b disease.
Purpose:
To study the factors affecting the risk of symptomatic temporal lobe necrosis after different fractionation schedules.
Methods and Materials:
One thousand thirty-two patients with T1-2 ...nasopharyngeal carcinoma treated with radical radiotherapy in Hong Kong during 1990–1995 were studied. They were treated at four different centers with similar techniques but different fractionation schedules: 984 patients were given 1 fraction daily throughout (q.d.), and 48 patients were irradiated twice daily (b.i.d.) for part of the course. The median total dose was 62.5 Gy (range 50.4–71.2), dose per fraction was 2.5 Gy (range 1.6–4.2), and overall treatment time (OTT) was 44 days (range 29–70). In addition, 500 patients received supplementary doses for parapharyngeal extension, 113 received booster doses by brachytherapy, and 114 received sequential chemotherapy using cisplatin-based regimes.
Results:
Altogether, 24 patients developed symptomatic temporal lobe necrosis: 18 from the q.d. group and 6 from the b.i.d. group. The 5-year actuarial incidence ranged from 0% (after 66 Gy in 33 fractions within 44 days) to 14% (after 71.2 Gy in 40 fractions within 35 days). Multivariate analyses showed that the risk was significantly affected by the fractional effect of the product of total dose and dose per fraction (hazard ratio HR = 1.04, 95% confidence interval CI 1.02–1.05), OTT (HR 0.88, 95% CI 0.80–0.97), and b.i.d. scheduling (HR 13, 95% CI 3–54). Repeating the analyses for patients treated with the q.d. schedules confirmed the independent significance of OTT in addition to the product of total dose and dose per fraction.
Conclusion:
The tentative results suggest that in addition to fractional dose, the OTT also had significant impact on the risk of temporal lobe necrosis, and b.i.d. scheduling increased the hazard further.
Objectives:
This prospective study aimed at investigating the efficacy and safety of the concurrent use of celecoxib (CXB) with 5-fluorouracil, epirubicin and cyclophosphamide (FEC), followed by ...docetaxel (T) in the neoadjuvant setting.
Patients and methods:
A total of 64 invasive breast cancer patients were recruited in the N001 Phase II, multicenter, open-label, single-arm study to receive four cycles of FEC (500, 100, 500 mg/m2) followed by four cycles of T (100 mg/m2) with concurrent CXB (200 mg b.i.d.) as neoadjuvant therapy (NAT). The combined chemotherapies were administered on day 1 of each cycle every 3 weeks. Primary endpoints were pathologic complete response (pCR) rate and objective response rate (ORR). Quasi-pCR (QpCR), pCR and near pCR (npCR) were discussed considering their similar survival outcomes. ORR included clinical complete response (cCR) and clinical partial response (cPR). Secondary endpoints included safety, breast conservation rate and disease-free survival.
Results:
Between February 2006 and January 2010, 57 of 64 evaluable patients with luminal A (n = 35, 61.4%), luminal B (n = 12, 21.1%), HER-2 positive (n = 8, 14%) and triple-negative (n = 2, 3.5%) breast cancer completed NAT and surgery. QpCR rate was observed in 18 (31.6%) patients. Exclusive of triple-negative subtype, pCR (p = 0.761) did not differ compared to other subtypes, while npCR (p = 0.043) exhibited a difference. Patients with HER-2 overexpression had a significantly higher QpCR than those of the disease attribute (10/20 vs 8/37, p = 0.029). After NAT, 43 (75.4%) and 13 (22.8%) patients achieved cCR and cPR, respectively. Patients responding to FEC were more likely to achieve a better ORR after subsequent T (p = 0.004). Over 80% of all patients received breast-conserving therapy (BCT) after receiving NAT, and 11 of 14 (78.6%) patients with T3 tumor at diagnosis became eligible for BCT after NAT. A total of 60 patients completed ≥ 6 cycles of NAT, followed by surgery; at a median follow-up of 50 months, 80% of the patients are disease-free. Neither drug-induced life-threatening toxicity nor cardiotoxicity was observed.
Conclusions:
Neoadjuvant use of FEC-T with concurrent CXB is active and safe for treatment of operable invasive breast cancer. The ORR was higher, but QpCR was comparable to other studies. Most patients are still disease-free, and BCT became an option for the females. Further clinical and translational studies on the use of cyclooxygenase-2 inhibitors with neoadjuvant chemotherapy are warranted.
Purpose: To study the treatment outcome in patients with locally recurrent nasopharyngeal carcinoma (NPC) and to explore whether a combination of high-dose-rate (HDR) intracavitary brachytherapy and ...external beam radiation therapy (ERT) could improve the therapeutic ratio.
Methods and Materials: Ninety-one patients with nonmetastatic locally recurrent NPC who were treated with curative intent during the years 1990–1999 were retrospectively analyzed. Eighty-two patients had histologically proven carcinoma. The remaining 9 had clinical and imaging features suggestive of local recurrence. The Ho’s T-stage distribution at recurrence (rT) was as follows: rT1–37, rT2–14, rT3–40. Total equivalent dose (TED) was calculated by the linear–quadratic formula without a time factor correction. For those treated by combined-modality treatment (CMT), the TED was taken as the summation of the equivalent dose by ERT and the absolute dose delivered to floor of the sphenoid by brachytherapy. Eight patients were treated solely with brachytherapy, all receiving 24–45 Gy in 3–10 sessions. Forty-one patients were treated with ERT alone receiving a median TED of 57.3 Gy (range, 49.8–62.5 Gy). Forty-two patients were treated by CMT with a median equivalent dose of 50 Gy (range, 40–60 Gy) given by ERT and 14.8 Gy by brachytherapy (range, 3–29.6 Gy). Multivariate analyses were performed using the Cox regression proportional hazards model.
Results: The 5-year actuarial overall survival rate, disease specific survival rate and local failure-free survival (LFFS) rate for the whole group were 30%, 33.3% and 37.8%, respectively. The 3-year LFFS rates of rT1, rT2, and rT3 diseases were 64%, 61.5%, and 18.4%, respectively (
p = 0.001).
Of the 8 patients treated with brachytherapy alone, 4 failed locally. Further analyses were concentrated on the ERT (41 patients) and CMT (42 patients) groups. The 3-year LFFS rates of rT1, rT2, and rT3 diseases were 66.7%, 66.7%, and 18.4%, respectively (
p = 0.0008). Better local control for patients who received a TED of 60 Gy or greater was shown. The corresponding 3-year LFFS rates were 29% and 60% (
p = 0.0004). Subgroup analysis on the ERT and CMT groups showed a 3-year LFFS rate of 33.5% and 57% (
p = 0.003). ERT group had an excess of patients with rT3 disease. Further analysis was performed on the rT1–2 patients showing a trend toward improvement in local control in favor of the CMT group (3-year LFFS rates: CMT, 71.7%; ERT, 54%;
p = 0.13). Multivariate analyses showed that rT stage (
p = 0.002) and TED (
p = 0.01; HR, 0.93; 95% confidence interval, 0.88–0.98) remained significant.
The 5-year major and central nervous system (CNS) complication-free rates were 26.7% and 47.8%. The following factors were found to be significant on univariate analyses for both complications in the ERT and CMT groups: (
1) Modality of treatment: more complications with ERT group; and (
2) rT stage. Multivariate analyses showed that the rT stage was significant for predicting the occurrence of major (
p = 0.004) and CNS complications (
p = 0.04).
Conclusion: For rT1–2 local recurrences, CMT with at least 60 Gy TED is recommended. The high incidence of major late complications is of serious concern. Ways of improving the local control of Ho’s rT3 disease and reducing the risk of late complications should be explored.
Purpose To evaluate the linguistic and psychometric properties of the Functional Living Index-Cancer (FLIC) in assessing the quality of life of Chinese cancer patients. Methods The English FLIC was ...translated into Traditional Chinese by the standard forward–backward procedure. After cognitive debriefing, a Traditional Chinese FLIC was administered to 500 cancer patients in a major public hospital in Hong Kong. Of which, 200 were invited to complete the questionnaire in 2 weeks. To identify a scale structure appropriate to Chinese, exploratory and confirmatory factor analyses were performed on two randomly split halves of the sample. Results We identified five scales of the Traditional Chinese FLIC which assess the physical, psychological, hardship, nausea and social aspects. These five scales and the overall scale demonstrated satisfactory fit and had the alpha coefficient ranged from 0.68 to 0.92. The intra-class correlation coefficient ranged from 0.67 to 0.88. In addition, all FLIC scales were negatively associated with the Eastern Cooperative Oncology Group performance status and, also except for the psychological scale, had lower scores in patients who were treated by chemotherapy. Conclusions The Traditional Chinese FLIC is an appropriate health indicator for Chinese cancer patients.
To define the dose–response relationship of nasopharyngeal carcinoma (NPC) above the conventional tumoricidal dose level of 66Gy when the basic radiotherapy (RT) course was given by the 2D Ho's ...technique.
Data from all five regional cancer centers in Hong Kong were pooled for this retrospective study. All patients (n=2426) were treated with curative-intent RT with or without chemotherapy between 1996 and 2000 with the basic RT course using the Ho's technique. The primary endpoint was local control. The prognostic significance of dose-escalation (‘boost’) after 66Gy, T-stage, N-stage, use of chemotherapy, sex and age (≤40 years vs >40 years) was studied. Both univariate and multivariate analyses were performed.
On multivariate analysis, T-stage (P< 0.01; hazard ratio HR, 1.58) and optimal boost (P=0.01; HR, 0.34) were the only significant factors affecting local failure for the whole study population, and for the population of patients treated by radiotherapy alone, but not for patients who also received chemotherapy. The following were independent determinants of local failure for patient groups with different T-stages treated by radiotherapy alone: use of a boost in T1/T2a disease (P=0.01; HR, 0.33); use of a boost (P<0.01; HR, 0.60) and age (P=0.01; HR, 1.02) in T3/T4 tumors. Among patients with T2b tumors treated by radiotherapy alone and given a boost, the use of a 20Gy-boost gave a lower local failure rate than a 10Gy-boost. There was no apparent excess mortality attributed to RT complications.
Within the context of a multi-center retrospective study, dose-escalation above 66Gy significantly improved local control for T1/T2a and T3/4 tumors when the primary RT course was based on the 2D Ho's technique without additional chemotherapy. ‘Boosting’ in NPC warrants further investigation. Caution should be taken when boosting is considered because of possible increase in radiation toxicity.
Purpose: To study the relative effects of different radiation factors on temporal lobe necrosis (TLN) and predictive accuracy of different biological equivalent models.
Methods and Materials: ...Consecutive patients (1008) treated radically with four different fractionation schedules during 1976–1985 for T1 nasopharyngeal carcinoma were retrospectively analyzed. All were irradiated by megavoltage photons using the same technique. Their age ranged from 18–84 years, and 92% of patients had complete follow-up. The fractional dose to inferomedial parts of both temporal lobes ranged from 2.5–4.2 Gy, total dose 45.6–60 Gy, and overall time 38–75 days.
Results: Despite a lower total dose of 50.4 Gy, the 621 patients irradiated with 4.2 Gy per fraction had a significantly higher incidence of temporal lobe necrosis than the 320 patients treated to 60 Gy with 2.5 Gy per fraction: the 10-year actuarial incidence being 18.6% vs. 4.6%,
p
< 0.001. Multivariate survival analysis showed that fractional effect (product of total dose and fractional dose) was the most significant factor:
p
= 0.0022, hazard ratio (HR) = 1.044 per Gy
2. Overall time and age were both insignificant. The α/β ratio calculated from our data was 2.9 Gy (95% CI: −1.8, 7.6 Gy). Biological effective dose (BED
Gy3), neuret, and brain tolerance unit all showed strongly significant correlation with the necrotic rate (
p
< 0.001), and gave similar predictions. The hazard of TLN increased by 14% per Gy
3, and it was estimated that 64 Gy (at conventional fractionation of 2 Gy daily) would lead to a 5% necrotic rate at 10 years. Not only did the nominal standard dose (NSD) show the lowest value in terms of log likelihood and standardized HR, but its predictions on TLN deviated markedly from clinically observed rates.
Conclusion: Fractional effect is the most significant factor affecting cerebral necrosis, and overall time has little protective effect. The BED formula, assuming an α/β ratio of 3 Gy, is an appropriate model for predicting late effects on the temporal lobe, and NSD could give seriously misleading predictions.
The study was aimed to introduce a design of a DICOM‐RT‐based tool box to facilitate 4D dose calculation based on deformable voxel‐dose registration. The computational structure and the calculation ...algorithm of the tool box were explicitly discussed in the study. The tool box was written in MATLAB in conjunction with CERR. It consists of five main functions which allow a) importation of DICOM‐RT‐based 3D dose plan, b) deformable image registration, c) tracking voxel doses along breathing cycle, d) presentation of temporal dose distribution at different time phase, and e) derivation of 4D dose. The efficacy of using the tool box for clinical application had been verified with nine clinical cases on retrospective‐study basis. The logistic and the robustness of the tool box were tested with 27 applications and the results were shown successful with no computational errors encountered. In the study, the accumulated dose coverage as a function of planning CT taken at end‐inhale, end‐exhale, and mean tumor position were assessed. The results indicated that the majority of the cases (67%) achieved maximum target coverage, while the planning CT was taken at the temporal mean tumor position and 56% at the end‐exhale position. The comparable results to the literature imply that the studied tool box can be reliable for 4D dose calculation. The authors suggest that, with proper application, 4D dose calculation using deformable registration can provide better dose evaluation for treatment with moving target.
PACS number(s): 87.55.kh
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