Prognostic value of sentinel node biopsy in 327 prospective melanoma patients from a single institution

Aim

To confirm the accuracy of sentinel node biopsy (SNB) procedure and its morbidity, and to investigate predictive factors for SN status and prognostic factors for disease-free survival (DFS) and disease-specific survival (DSS).

Materials and methods

Between October 1997 and December 2004, 327 consecutive patients in one centre with clinically node-negative primary skin melanoma underwent an SNB by the triple technique, i.e. lymphoscintigraphy, blue-dye and gamma-probe. Multivariate logistic regression analyses as well as the Kaplan–Meier were performed.

Results

Twenty-three percent of the patients had at least one metastatic SN, which was significantly associated with Breslow thickness (p < 0.001). The success rate of SNB was 99.1% and its morbidity was 7.6%. With a median follow-up of 33 months, the 5-year DFS/DSS were 43%/49% for patients with positive SN and 83.5%/87.4% for patients with negative SN, respectively. The false-negative rate of SNB was 8.6% and sensitivity 91.4%. On multivariate analysis, DFS was significantly worsened by Breslow thickness (RR = 5.6, p < 0.001), positive SN (RR = 5.0, p < 0.001) and male sex (RR = 2.9, p = 0.001). The presence of a metastatic SN (RR = 8.4, p < 0.001), male sex (RR = 6.1, p < 0.001), Breslow thickness (RR = 3.2, p = 0.013) and ulceration (RR = 2.6, p = 0.015) were significantly associated with a poorer DSS.

Conclusion

SNB is a reliable procedure with high sensitivity (91.4%) and low morbidity. Breslow thickness was the only statistically significant parameter predictive of SN status. DFS was worsened in decreasing order by Breslow thickness, metastatic SN and male gender. Similarly DSS was significantly worsened by a metastatic SN, male gender, Breslow thickness and ulceration. These data reinforce the SN status as a powerful staging procedure.     

Lymph node ratio is an independent prognostic factor in patients with rectal cancer treated with preoperative chemoradiotherapy and curative resection

Purpose

To evaluate the prognostic effect of lymph node ratio (LNR) in patients with locally advanced rectal cancer who were treated with curative resection after preoperative chemoradiotherapy (CRT).

Methods

Between October 2001 and December 2007, 519 patients who had undergone curative resection of primary rectal cancer after preoperative CRT were enrolled. Of these, 154 patients were positive for lymph node (LN) metastasis and were divided into three groups according to the LNR (≤0.15 [n = 80], 0.16–0.3 [n = 44], >0.3 [n = 30]) to evaluate the prognostic effect on overall survival (OS) and disease-free survival (DFS).

Results

LNR (≤0.15, 0.16–0.3, and >0.3) was significantly associated with 5-year OS (90.3%, 75.1%, and 45.1%; p < 0.001) and DFS (66.7%, 55.8%, and 21.9%; p < 0.001) rates. In a multivariate analysis, LNR (≤0.15, 0.16–0.3, and >0.3) was a significant independent prognostic factor for OS (hazard ratios [HRs], 1, 3.609, and 8.197; p < 0.001) and DFS (HRs, 1, 1.699, and 3.960; p < 0.001). LNR had a prognostic impact on OS and DFS in patients with <12 harvested LNs, as well as in those with ≥12 harvested LNs (p < 0.05).

Conclusion

LNR was a significant independent prognostic predictor for OS and DFS in patients with locally advanced rectal cancer who were treated with curative resection after preoperative CRT.     

Quality of care indicators and their related outcomes: A population-based study in prostate cancer patients treated with radiotherapy

Background and purpose

We describe variations across the regional cancer centres in Ontario, Canada for five prostate cancer radiotherapy (RT) quality indicators: incomplete pre-treatment assessment, follow-up care, leg immobilization, bladder filling, and portal film target localization. Along with cancer centre volume, we examined each indicator’s association with relevant outcomes: long-term cause-specific survival, urinary incontinence, and gastrointestinal and genitourinary late morbidities.

Materials and methods

We conducted a population-based retrospective cohort study of 924 prostate cancer patients diagnosed between 1990 and 1998 who received RT within 9 months of diagnosis. Data sources included treating charts and registry and administrative data. The associations between indicators and outcomes were analysed using regression techniques to control for potential confounders.

Results

Practice patterns varied across the regional cancer centres for all indicators (p < 0.0001). Incomplete pre-treatment assessment was associated with worse cause-specific survival although this result was not significant when adjusted for confounding (adjusted RR = 1.78, 95% CI = 0.79–3.98). Treatment without leg immobilization (adjusted RR = 1.72, 95% CI = 1.16–2.56) and with an empty bladder (adjusted RR = 1.98, 95% CI = 1.08–3.63) was associated with genitourinary late morbidities. Treatment without leg immobilization was also associated with urinary incontinence (adjusted RR = 2.18, 95% CI = 1.23–3.87).

Conclusions

We documented wide variations in practice patterns. We demonstrated that measures of quality of care can be shown to be associated with clinically relevant outcomes in a population-based sample of prostate cancer patients.     

The prognostic significance of extracapsular lymph node involvement in node positive patients with colonic cancer

Aims

In colonic cancer the prognostic significance of extracapsular lymph node involvement (LNI) is not established and is therefore the objective of this study.

Methods

Between January 1994 and May 2005, all patients who underwent resection for primary colonic cancer with lymph node metastasis were reviewed. All resected lymph nodes were re-examined to assess extracapsular LNI. In uni- and multivariate analysis disease-free survival (DFS) was correlated with various clinicopathologic factors.

Results

One hundred and eleven patients were included. In 58 patients extracapsular LNI was identified. Univariate analysis revealed that pN-stage (5-year DFS pN1 vs. pN2: 65% vs. 14%, p < 0.001), extracapsular LNI (5-year DFS intracapsular LNI vs. extracapsular LNI: 69% vs. 41%, p = 0.003), and lymph node ratio (5-year DFS <0.176 vs. ≥0.176: 67% vs. 42%, p = 0.023) were significant prognostic indicators. Among these variables pN-stage (hazard ratio 3.5, 95% confidence interval [CI]: 1.72–7.42) and extracapsular LNI (hazard ratio 1.98, 95% CI: 1.00–3.91) were independent prognostic factors. Among patients without extracapsular LNI, those receiving adjuvant chemotherapy had a significantly better survival (p = 0.010). In contrast, chemotherapy did not improve DFS in patients with extracapsular LNI.

Conclusion

Together with pN2 stage, extracapsular LNI reflects a particularly aggressive behaviour and has significant prognostic potential.     

Recombinant human thyrotropin-aided versus thyroid hormone withdrawal-aided radioiodine treatment for differentiated thyroid cancer after total thyroidectomy: A meta-analysis

Background and purpose

We conducted a meta-analysis of randomized controlled trials (RCTs) to compare the effects of recombinant human thyrotropin (rhTSH) and thyroid hormone withdrawal (THW) on thyrotropin stimulation prior to remnant ablation of differentiated thyroid cancer (DTC).

Material and methods

A comprehensive search was conducted for articles discussing rhTSH and THW prior to December 2012. After applying the inclusion criteria, all the available data were summarized to analyze the efficacy of rhTSH and THW for stimulating TSH.

Results

Seven RCTs that involved a total of 1535 patients, were included in the analysis. The ablation rates of the rhTSH group and the THW group were not significantly different (RR = 0.97, 95% CI: 0.94–1.01, p = 0.1). Patients in the rhTSH group had a better quality of life (QoL) than those in the THW group on the day of ablation (RR = 3.92, 95% CI: 3.44–5.40, p < 0.00001). However, there was no difference in the QoL 3 months after ablation (RR = −0.9, 95% CI: −2.20–0.39, p = 0.17). Additionally, there were no significant differences in serum thyroglobulin (Tg) levels measured just before radioiodine remnant ablation (preablation thyroglobulin levels) (RR = −0.14, 95% CI: −0.73–0.45, p = 0.65), or in days of hospital isolation (RR = −10.51, 95% CI: −32.79–11.73, p = 0.35)

Conclusions

Our findings indicate that the administration of rhTSH had resulted in an ablation rate similar to that of THW for DTC patients, but rhTSH provided a better QoL at the time of ablation.     

Equivalent survival in patients with advanced stage IB–II and III–IVA cervical cancer treated by adjuvant surgery following chemoradiotherapy

Objectives

To evaluate survival in patients with advanced cervical cancer who underwent surgery after concurrent chemoradiotherapy.

Methods

One hundred and forty-four patients with biopsy-proven stage IB–IVA cervical cancer underwent adjuvant surgery after concurrent chemoradiotherapy. Surgical resection was classified as curative (no evidence of remaining disease after surgery) or palliative (remaining disease after surgery). Endpoints were pelvic control, overall survival (OS) and disease-free survival (DFS) at 5 and 10 years. Analysis included tumour FIGO stage, type of surgery (curative versus palliative), pelvic control, response to chemoradiotherapy and lymphatic status.

Results

Tumour FIGO stages were IB–II in 91 cases and III–IVA in 53 cases. Surgery was curative in 127 cases. Pelvic control was achieved in 114 patients and was equivalent in stage IB–II and III–IVA patients. So far, 60 patients have died. The 5-year OS and DFS rates were, respectively, 57.6% [95% CI: 49.1–67.5] and 65% [95% CI: 56.2–75]. OS was significantly affected by the type of surgery (p < 2.10⁻¹⁶), the presence of tumoural residue (p = 0.002) and the pelvic lymphatic status (p < 0.001). DFS was affected by the pelvic (p = 0.02) and para-aortic lymphatic status (p = 0.009). No significant difference was observed between OS and DFS in stage IB–II and III–IVA patients, whereas a macroscopic tumoural residue was observed in, respectively, 30.9 and 52.2% of cases (p = 0.022).

Conclusion

Survival rates were equivalent between patients with IB–II and III–IVA cervical cancer, suggesting that adjuvant surgery following chemoradiotherapy may improve local control.     

Referral bias in thyroid cancer surgery: Direction and magnitude

Aim

This study was conducted to clarify the impact of referral bias in thyroid cancer surgery.

Methods

Analysis of 1419 consecutive patients with papillary (n = 653), follicular (n = 248), and medullary thyroid cancer (n = 518) referred to a specialist center for initial surgery or reoperation.

Results

With increasing travel distance (successive postal code areas), mean age decreased among patients referred for initial surgery (from 53 to 35 years for papillary cancer, 65 to 49 years for sporadic medullary cancer, and 40 to 23 years for hereditary medullary cancer, all p ≤ 0.001; and from 65 to 54 years for follicular cancer, p = 0.26). The significant decline in mean age continued among patients reoperated on for papillary cancer (from 53 to 43 years, p < 0.001), but was lost among patients reoperated on for medullary cancers.For patients with differentiated, but not medullary cancers, greater travel distance was associated with higher frequencies of extrathyroidal extension at initial surgery (from 17% to 63% for follicular cancer, p = 0.003) and reoperation (from 18% to 47% for papillary, and 5% to 44% for follicular cancer, all p < 0.001), and higher frequencies of lymph node metastasis at initial surgery (from 23% to 58% for papillary, and 17% to 50% for follicular cancer, p ≤ 0.008) and reoperation (from 27% to 77% for papillary, and 0% to 35% for follicular cancer, all p < 0.001).

Conclusion

Referral bias in thyroid cancer surgery can include two components working in opposite directions: age and extent of disease. Controlling for these components should reduce the impact of referral bias on thyroid cancer research.     

Adjuvant extension of chemotherapy after neoadjuvant therapy may not improve outcome in early-stage breast cancer

Introduction

Neoadjuvant chemotherapy (NAC) is equivalent to adjuvant therapy (AdC) in terms of survival and disease-free interval. Many institutions add AdC after NAC and surgery. However, such extended chemotherapy (ExC) is not evidence based. Study aim was to investigate if ExC improved disease-free (DFS) and overall survival (OS).

Patients and Methods

From 1998 to 2006 356 consecutive patients received NAC (45 pts), AdC (221 pts) or ExC (90 pts). We analysed these 3 groups to determine effects of ExC and to identify patients who might benefit. NAC consisted in 93% of 3–6 cycles of epirubicin + docetaxel, AdC comprised EC ± taxanes in 72%. Median age in the NAC, AdC, and ExC-groups was 54, 56 and 52 years with follow-up of 30, 57, and 55 months.

Results

After NAC, 35% achieved downstaging and 10% pathologic complete remission. Surprisingly ExC seemed to result in reduction of 5-year DFS: compared to 85% and 82% after NAC and AdC, DFS was 61% after ExC (p = 0.001). OS was not significantly affected (79, 91, and 78% after NAC, AdC and ExC, p = 0.13). In multivariate analysis after correction for age, menopausal status, stage, grading, hormone receptors, her2-status, radiotherapy and surgery, ExC seemed to adversely affect DFS (HR 2.15, p = 0.008), loco-regional and distant recurrence-rates (HR 3.0, p = 0.03 and HR 2.0, p = 0.02).

Discussion

In this single-center analysis ExC could not show advantages in terms of DFS and OS. Because multivariate analyses of retrospective data cannot account for all potential biases, these data require confirmation in randomized clinical trials. Until then, extended chemotherapy should be considered carefully. As in previous studies, no differences were found between NAC and AdC groups.     

Lymph node micrometastasis in node negative early gastric cancer

Aims

The clinical significance of lymph node micrometastasis for histologically node negative gastric cancer is not well documented. This study was to assess the incidence and to clarify the risk factors of lymph node micrometastasis in patients with node negative early gastric cancer (EGC).

Methods

We investigated the lymph node micrometastasis with using an anticytokeratin immunohistochemical stain in 90 patients with node negative EGC who underwent curative resection between 1991 and 2000.

Results

Among 3526 nodes from 90 patients, there were 17 cytokeratin immunohistochemical stain positive nodes from nine patients. The incidence of micrometastasis was higher in patients with lymphatic invasion (p = 0.012), venous invasion (p = 0.026) and larger tumor (p = 0.003). The independent risk factors for lymph node micrometastasis were lymphatic invasion (p = 0.004, RR = 22.915, 95% CI = 2.709 ∼ 193.828) and tumor size (p = 0.029, RR = 1.493, 95% CI = 1.042 ∼ 2.138). Although there were 10 deaths during the follow-up period of mean 67.6 months (1 month ∼ 147 months), there was no death from a cancer recurrence.

Conclusions

The incidence of lymph node micrometastasis in patients with node negative early gastric cancer was 10%, and the independent risk factors for micrometastasis were lymphatic invasion and tumor size.     

Cross-validation analysis of the prognostic significance of mucin expression in patients with resected non-small cell lung cancer treated with adjuvant chemotherapy: Results from IALT,JBR.10 and ANITA

Introduction

CALGB 9633 was a randomized trial of observation versus adjuvant chemotherapy for patients with stage IB non-small cell lung cancer (NSCLC). In CALGB 9633, the presence of mucin in the primary tumor was associated with shorter disease-free survival (DFS; hazard ratio (HR) = 1.9, p = 0.002) and overall survival (OS; HR = 1.9, p = 0.004).

Methods

To validate these results, mucin staining was performed on primary tumor specimens from 780 patients treated on IALT, 351 on JBR.10 and 150 on ANITA. The histochemical technique using mucicarmine was performed. The prognostic value of mucin for DFS and OS was tested in a Cox model stratified by trial and adjusted for clinical and pathological factors. A pooled analysis of all 4 trials was performed for the predictive value of mucin for benefit from adjuvant chemotherapy.

Results

The cross-validation group had 48% squamous, 37% adenocarcinoma and 15% other NSCLC compared with 29%, 56%, and 15%, respectively in CALGB. Among 1262 patients with assessable results, mucin was positive in IALT 24%, JBR.10 30%, ANITA 22% compared with 45% in CALGB. Histology was the only significant covariate (p < 0.0001) in multivariate analysis with mucin seen more commonly in adenocarcinoma (56%) compared with squamous (5%) and other NSCLC (15%). Mucin was a borderline negative prognostic factor for DFS (HR = 1.2 [1.0–1.5], p = 0.06) but not significantly so for OS (HR = 1.1 [0.9–1.4], p = 0.25). Prognostic value did not vary according to histology: HR = 1.3 [1.0–1.6] in adenocarcinoma vs. 1.6 [1.2–2.2] for DFS in other histology (interaction p = 0.69). Mucin status was not predictive for benefit from adjuvant chemotherapy (test of interaction: DFS p = 0.27; OS p = 0.49).

Conclusions

Mucin was less frequent in the cross-validation group due to its higher percentage of squamous cell carcinomas. The negative impact of mucin was confirmed for DFS but not for OS. Mucin expression was not predictive of overall survival benefit from adjuvant chemotherapy.     

Is there a relation between the radiation dose to the different sub-segments of the lower urinary tract and urinary morbidity after brachytherapy of the prostate with I-125 seeds?

Background and Purpose

To investigate possible relationships between the dose to the sub-segments of the lower urinary tract and lower urinary tract symptoms (LUTS) after brachytherapy of the prostate.

Materials and Methods

This study involved 225 patients treated for prostate cancer with I-125 seeds. Post-implant dose-volume histograms of the prostate, urethra, bladder wall, bladder neck and external sphincter were determined. Endpoints were the mean and the maximum International Prostate Symptom Score (IPSS) during the first 3 months after the treatment. For binary analysis the patients were stratified in a group with enhanced LUTS and a group with non-enhanced LUTS.

Results

The dose to 0.5 cm³ of the bladder neck ‘D_0.5cc-blne’ (p = 0.002 and p = 0.005), the prostate volume prior to treatment ‘V_pr-0’ (p = 0.005 and p = 0.024) and the pre-treatment IPSS (both p < 0.001) were independently correlated with mean and maximum IPSS, respectively. Of the patients with a D_0.5cc-blne ? 175 Gy and a V_pr-0 ? 42 cm³, 68% suffered from enhanced LUTS, against just 30% of the other patients (p < 0.0001).

Conclusions

Pre-treatment IPSS, prostate volume and dose to the bladder neck are correlated with post-implant IPSS. A combination of a large prostate and a high dose to the bladder neck is highly predictive for enhanced early LUTS.     

Prognostic factors and assessment of staging systems for head and neck soft tissue sarcomas in adults

Objectives

The primary objectives of this study were to analyse the outcome of patients diagnosed with head and neck soft tissue sarcomas (HNSTS) and to identify relevant prognostic factors. As well as this, we compared the prognostic value of two staging systems proposed by the American Joint Committee on Cancer (AJCC) and the Memorial Sloan-Kettering Cancer Center (MSKCC).

Methods

From 07/1988 to 01/2008, the charts of 42 adult patients were retrospectively reviewed. Potential prognostic factors were analysed according to overall survival (OS), disease-free survival (DFS) and disease-specific survival (DSS).

Results

At 5 years, OS was 57%, DFS 47% and DSS 72%. On univariate analysis, statistically significant prognostic factors were for OS, distant or lymph node metastasis at diagnosis (p = 0.032), for DFS, margins after surgery (p = 0.007), for DSS, regional or distant metastasis at diagnosis (p = 0.002), initial AJCC and MSKCC stage (p = 0.018 and p = 0.048) and margins after surgery (p = 0.042). On multivariate analysis, margins remained statistically significant for DFS (p = 0.039) when there was a trend with the initial AJCC stage (p = 0.054) for OS. The AJCC staging system was of more prognostic value than the MSKCC staging system.

Conclusions

Achieving clear margins after surgery is vital for improved local control and the best chance of survival. Adjuvant chemotherapy and radiotherapy were not shown to provide additional benefit. To better identify prognostic factors, it seems essential to set up national and international databases allowing multicenter registration for those patients.     

The clinical outcome and prognostic factors after multi-visceral resection for advanced colon cancer

Aim

The value of multi-visceral resection (MVR) for treating primary advanced colon cancer infiltrating into the neighboring organs had been debated because of the high mortality.

Methods

We reviewed 1288 patients who underwent curative resection for pT3–4 colon cancer without distant metastasis from 1994 to 2004.

Results

Eighty four patients (6.5%) with colon cancer infiltrating into the neighboring organs (cT4) underwent MVR. The accuracy of the intra-operative decision for true invasion (pT4) was 35.7%. Major surgical morbidity occurred in 11 patients of the standard resection group (0.9%) and in 2 patients of the MVR group (2.3%) (p = 0.206). Most of the recurrence was distant metastasis (20 patients, 23.8%). Local recurrence was occurred in five patients (6.0%). The prognostic factors for recurrence and survival were pathologic tumor invasion (p = 0.033 and p = 0.016, respectively) and lymph node metastasis (p = 0.010 and p < 0.001, respectively).

Conclusion

Multi-visceral resection was a safe and curative procedure as compared with standard resection for patients with advanced colon cancer. The cause of a poor prognosis in MVR was not local recurrence but distant metastasis. Pathologic tumor invasion and lymph node metastasis were the potential prognostic factors.     

Risk of cardiac dysfunction with trastuzumab in breast cancer patients: a meta-analysis

Background

Trastuzumab is used widely for the treatment of early and advanced breast cancer. However, concerns have arisen regarding its cardiac toxicity. We did a systematic review and meta-analysis of published randomized controlled trials (RCTs) to assess the overall risk of cardiac dysfunction associated with trastuzumab treatment.

Methods

We searched PubMed and Web of Science (January 1966-July 2009) and American Society of Clinical Oncology conferences held (January 2000-July 2009) for relevant articles and abstracts. Summary incidence rates, relative risks (RRs), and 95% confident intervals (CIs) were calculated using a fixed-effects or random-effects model.

Results

11,882 patients from 10 RCTs were included for analysis. The incidences of LVEF decrease and congestive heart failure (CHF) were 7.5% (95% CI 4.2-13.1) and 1.9% (95% CI 1.0-3.8) among patients receiving trastuzumab. Trastuzumab significantly increased the risk of LVEF decrease (RR = 2.13, 95% CI, 1.31-3.49; p = 0.003). In addition, it significantly increased the risk of CHF (RR = 4.19, 95% CI 2.73-6.42; p < 0.00001). The increased risk of CHF was observed in patients with early stage (RR = 4.05, 95% CI 2.49-6.58; p < 0.00001) as well as metastatic disease (RR = 4.75, 95% CI 1.93-11.71; p = 0.0007). Furthermore, trastuzumab significantly increased the risk of CHF (RR = 4.27, 95% CI 2.75-6.61, p < 0.00001) in patients receiving anthracycline-based chemotherapy, but not in patients receiving non-anthracycline chemotherapy (RR = 2.42, 95% CI 0.36-16.19, p = 0.36).

Conclusion

The addition of trastuzumab to anthracycline-based chemotherapy significantly increase the risk of cardiac dysfunction in breast cancer patients. Further studies are recommended for non-anthracycline chemotherapy.     

Hypofractionated whole breast irradiation for patients with large breasts: A randomized trial comparing prone and supine positions

Background and purpose

Comparison of acute toxicity of whole-breast irradiation (WBI) in prone and supine positions.

Materials and methods

This non-blinded, randomized, prospective, mono-centric trial was undertaken between December 29, 2010, and December 12, 2012. One hundred patients with large breasts were randomized between supine multi beam (MB) and prone tangential field (TF) intensity modulated radiotherapy (IMRT). Dose–volume parameters were assessed for the breast, heart, left anterior descending coronary artery (LAD), ipsilateral lung and contralateral breast. The primary endpoint was acute moist skin desquamation. Secondary endpoints were dermatitis, edema, pruritus and pain.

Results

Prone treatment resulted in: improved dose coverage (p < 0.001); better homogeneity (p < 0.001); less volumes of over-dosage (p = 0.001); reduced acute skin desquamation (p < 0.001); a 3-fold decrease of moist desquamation p = 0.04 (chi-square), p = 0.07 (Fisher’s exact test)); lower incidence of dermatitis (p < 0.001), edema (p = 0.005), pruritus (p = 0.06) and pain (p = 0.06); 2- to 4-fold reduction of grades 2–3 toxicity; lower ipsilateral lung (p < 0.001) and mean LAD (p = 0.007) dose; lower, though statistically non-significant heart and maximum LAD.

Conclusions

This study provides level I evidence for replacing the supine standard treatment by prone IMRT for whole-breast irradiation in patients with large breasts. A confirmatory trial in a multi-institutional setting is warranted.     

Comparison of concomitant boost radiotherapy against concurrent chemoradiation in locally advanced oropharyngeal cancers: A phase III randomised trial

Purpose

To test the toxicity and efficacy of concomitant boost radiotherapy alone against concurrent chemoradiation (conventional fractionation) in locally advanced oropharyngeal cancer in our patient population.

Methods and materials

In this open-label, randomised trial, 216 patients with histologically proven Stage III–IVA oropharyngeal cancer were randomly assigned between June 2006 and December 2010 to receive either chemoradiation (CRT) to a dose of 66 Gy in 33 fractions over 6.5 weeks with concurrent cisplatin (100 mg/m² on days 1, 22 and 43) or accelerated radiotherapy with concomitant boost (CBRT) to a dose of 67.5 Gy in 40 fractions over 5 weeks. The compliance, toxicity and quality of life were investigated. Disease-free survival (DFS) and overall survival (OS) curves were estimated with the Kaplan–Meier method and compared using log rank test.

Results

The compliance to radiotherapy was superior in concomitant boost with lesser treatment interruptions (p = 0.004). Expected acute toxicities were significantly higher in CRT, except for grade 3/4 mucositis which was seen more in CBRT arm (39% and 55% in CRT and CBRT, respectively; p = 0.02). Late toxicities like Grade 3 xerostomia were significantly high in CRT arm than CBRT arm (33% versus 18%; p < 0.0001). The quality of life was significantly poor in CRT arm at all follow up visits (p < 0.0001). The rates of 2 year disease-free survival were similar with 56% in the chemoradiotherapy group and 61% in CBRT group (p = 0.2; HR-0.81, 95%CI-0.53–1.2). Subgroup analysis revealed that patients with nodal size >2 cm had significantly better DFS with CRT (p = 0.05; HR-1.59, 95%CI-0.93–2.7).

Conclusion

In selected patients of locally advanced oropharyngeal cancer, concomitant boost offers a better compliance, toxicity profile and quality of life with similar disease control, than chemoradiation.     

Improved robotic stereotactic body radiation therapy plan quality and planning efficacy for organ-confined prostate cancer utilizing overlap-volume histogram-driven planning methodology

Background and purpose

This study is to determine if the overlap-volume histogram (OVH)-driven planning methodology can be adapted to robotic SBRT (CyberKnife Robotic Radiosurgery System) to further minimize the bladder and rectal doses achieved in plans manually-created by clinical planners.

Methods and materials

A database containing clinically-delivered, robotic SBRT plans (7.25 Gy/fraction in 36.25 Gy) of 425 patients with localized prostate cancer was used as a cohort to establish an organ’s distance-to-dose model. The OVH-driven planning methodology was refined by adding the PTV volume factor to counter the target’s dose fall-off effect and incorporated into Multiplan to automate SBRT planning. For validation, automated plans (APs) for 12 new patients were generated, and their achieved dose/volume values were compared to the corresponding manually-created, clinically-delivered plans (CPs). A two-sided, Wilcoxon rank-sum test was used for statistical comparison with a significance level of p < 0.05.

Results

PTV’s V(36.25 Gy) was comparable: 95.6% in CPs comparing to 95.1% in APs (p = 0.2). On average, the refined approach lowered V(18.12 Gy) to the bladder and rectum by 8.2% (p < 0.05) and 6.4% (p = 0.14). A physician confirmed APs were clinically acceptable.

Conclusions

The improvements in APs could further reduce toxicities observed in SBRT for organ-confined prostate cancer.     

Serum reactive oxygen species modulator 1 (Romo1) as a potential diagnostic biomarker for non-small cell lung cancer

Objectives

Reactive oxygen species modulator 1 (Romo1) is a novel protein that localizes in the mitochondrial membrane and induces mitochondrial reactive oxygen species (ROS) generation. Romo1 is increased in most cancer cell lines and is related with resistance to chemotherapy in vitro. However, data on its expression in patients with malignancy is very limited. We evaluated the usefulness of serum Romo1 as a potential diagnostic biomarker in non-small cell lung cancer (NSCLC).

Materials and methods

We initially assessed the expression of Romo1 using Western blotting and enzyme-linked immunosorbent assay in paired lung tissue and serum specimen from NSCLC patients who underwent surgical resection. Then we evaluated and compared serum Romo1 level in a healthy population (n = 55), patients with benign lung diseases (n = 63) and NSCLC patients (n = 58). We explored the correlation between Romo1 expression and clinical parameters and assessed diagnostic performance of serum Romo1 for NSCLC using receiver operating characteristic (ROC) curve analysis.

Results

Romo1 expression in lung cancer tissues was significantly increased compared with non-tumorous tissues (p < 0.001). Romo1 expression in cancer tissues positively correlated with that in serum (r = 0.68, p = 0.009). Serum Romo1 level in NSCLC patients significantly increased compared with that of healthy population or patients with benign lung diseases (both p < 0.001). ROC curve analysis using an optimal cutoff value of 329.7 pg/mL revealed sensitivity and specificity for the diagnosis of NSCLC of 81.9% and 89.8%, respectively, with an area under the curve of 0.847 (95% confidence interval: 0.789–0.892, p < 0.001). Serum Romo1 level was not related with age, gender, smoking status, tumor differentiation, histological type or stage.

Conclusions

Serum Romo1 discriminated NSCLC patients from the population without cancer with considerable sensitivity and specificity. Serum Romo1 could be a potential diagnostic biomarker for NSCLC.