Diagnostic and prognostic correlates of preoperative FDG PET for breast cancer.

PURPOSE: To explore the preoperative utility of FDG PET for the diagnosis and prognosis in a retrospective breast cancer case series. METHODS: In this retrospective study, 104 patients who had undergone a preoperative FDG PET scan for primary breast cancer at the UZ Brussel during the period 2002-2008 were identified. Selection criteria were: histological confirmation, FDG PET performed prior to therapy, and breast surgery integrated into the primary therapy plan. Patterns of increased metabolism were recorded according to the involved locations: breast, ipsilateral axillary region, internal mammary chain, or distant organs. The end-point for the survival analysis using Cox proportional hazards was disease-free survival. The contribution of prognostic factors was evaluated using the Akaike information criterion and the Nagelkerke index. RESULTS: PET positivity was associated with age, gender, tumour location, tumour size >2 cm, lymphovascular invasion, oestrogen and progesterone receptor status. Among 63 patients with a negative axillary PET status, 56 (88.9 %) had three or fewer involved nodes, whereas among 41 patients with a positive axillary PET status, 25 (61.0 %) had more than three positive nodes (P < 0.0001). In the survival analysis of preoperative characteristics, PET axillary node positivity was the foremost statistically significant factor associated with decreased disease-free survival (hazard ratio 2.81, 95% CI 1.17-6.74). CONCLUSION: Preoperative PET axillary node positivity identified patients with a higher burden of nodal involvement, which might be important for treatment decisions in breast cancer patients.

Health-related quality of life in survivors of stage I-II breast cancer: randomized trial of post-operative conventional radiotherapy and hypofractionated tomotherapy.

BACKGROUND: Health-related quality of life (HRQOL) assessment is a key component of clinical oncology trials. However, few breast cancer trials comparing adjuvant conventional radiotherapy (CR) and hypofractionated tomotherapy (TT) have investigated HRQOL. We compared HRQOL in stage I-II breast cancer patients who were randomized to receive either CR or TT. Tomotherapy uses an integrated computed tomography scanner to improve treatment accuracy, aiming to reduce the adverse effects of radiotherapy. METHODS: A total of 121 stage I-II breast cancer patients who had undergone breast conserving surgery (BCS) or mastectomy (MA) were randomly assigned to receive either CR or TT. CR patients received 25 × 2 Gy over 5 weeks, and BCS patients also received a sequential boost of 8 × 2 Gy over 2 weeks. TT patients received 15 × 2.8 Gy over 3 weeks, and BCS patients also received a simultaneous integrated boost of 15 × 0.6 Gy over 3 weeks. Patients completed the EORTC QLQ-C30 and BR23 questionnaires. The mean score (± standard error) was calculated at baseline, the end of radiotherapy, and at 3 months and 1, 2, and 3 years post-radiotherapy. Data were analyzed by the 'intention-to-treat' principle. RESULTS: On the last day of radiotherapy, patients in both treatment arms had decreased global health status and functioning scores; increased fatigue (clinically meaningful in both treatment arms), nausea and vomiting, and constipation; decreased arm symptoms; clinically meaningful increased breast symptoms in CR patients and systemic side effects in TT patients; and slightly decreased body image and future perspective. At 3 months post-radiotherapy, TT patients had a clinically significant increase in role- and social-functioning scores and a clinically significant decrease in fatigue. The post-radiotherapy physical-, cognitive- and emotional-functioning scores improved faster in TT patients than CR patients. TT patients also had a better long-term recovery from fatigue than CR patients. ANOVA with the Bonferroni correction did not show any significant differences between groups in HRQOL scores. CONCLUSIONS: TT patients had a better improvement in global health status and role- and cognitive-functioning, and a faster recovery from fatigue, than CR patients. These results suggest that a shorter fractionation schedule may reduce the adverse effects of treatment.

Scapula alata in early breast cancer patients enrolled in a randomized clinical trial of post-surgery short-course image-guided radiotherapy.

BACKGROUND: Scapula alata (SA) is a known complication of breast surgery associated with palsy of the serratus anterior, but it is seldom mentioned. We evaluated the risk factors associated with SA and the relationship of SA with ipsilateral shoulder/arm morbidity in a series of patients enrolled in a trial of post-surgery radiotherapy (RT). METHODS: The trial randomized women with completely resected stage I-II breast cancer to short-course image-guided RT, versus conventional RT. SA, arm volume and shoulder-arm mobility were measured prior to RT and at one to three months post-RT. Shoulder/arm morbidities were computed as a post-RT percentage change relative to pre-RT measurements. RESULTS: Of 119 evaluable patients, 13 (= 10.9%) had pre-RT SA. Age younger than 50 years old, a body mass index less than 25 kg/m2, and axillary lymph node dissection were significant risk factors, with odds ratios of 4.8 (P = 0.009), 6.1 (P = 0.016), and 6.1 (P = 0.005), respectively. Randomization group was not significant. At one to three months' post-RT, mean arm volume increased by 4.1% (P = 0.036) and abduction decreased by 8.6% (P = 0.046) among SA patients, but not among non-SA patients. SA resolved in eight, persisted in five, and appeared in one patient. CONCLUSION: The relationship of SA with lower body mass index suggests that SA might have been underestimated in overweight patients. Despite apparent resolution of SA in most patients, pre-RT SA portended an increased risk of shoulder/arm morbidity. We argue that SA warrants further investigation. Incidentally, the observation of SA occurring after RT in one patient represents the second case of post-RT SA reported in the literature.

Pre-OPerative accelerated radiotherapy for early stage breast cancer patients (POPART): A feasibility study.

Pre-operative 5-fraction breast radiotherapy followed by immediate breast-sparing surgery and sentinel node procedure was feasible in 14 patients with 15 clinical early-stage breast cancers. However wound problems occurred frequently and was documented in 5 of the 14 patients: 2 patients with a mastitis needing antibiotics, 2 patients developed a fistula with exudate needing antibiotics and local disinfection and 1 patient developed a fistula needing surgical reintervention. Other acute and late iatrogenic events were rather limited. Two patients had a pathological lymph node involvement, which underlines the importance to perform the sentinel node procedure before pre-operative radiotherapy.

Pattern of failure after helical tomotherapy in head and neck cancer.

BACKGROUND AND PURPOSE: Helical tomotherapy (HT, Hi-Art TomoTherapy(®)) is a recently developed radiation device delivering highly conformal dose with a rotational gantry resulting in more uniform target doses and better avoidance of organs at risk. Treatment failure patterns in head and neck cancer (HNC) patients treated with HT were analyzed. PATIENTS AND METHODS: 63 patients with a biopsy-proven HNC were treated with HT. In patients with locoregional failure, the volume of failure (Vf) was contoured and co-registered with the initial planning computed tomography scan. With the use of dose-volume histogram (DVH) analysis, the Vf was classified as "in-field" (InF), "marginal" (MF) or "outside-field" (OutF), if ≥ 95%, 20-94%, and < 20% of Vf, respectively, were within the 95% isodose. RESULTS: Median follow-up time was 25 months (95% confidence interval 19.4-28 months). 2-year overall survival, disease-free survival, and locoregional control were 66%, 54%, and 77%, respectively. 13 patients developed a locoregional failure (four local, eight regional, and one local and regional). After DVH analysis, there were ten InF and two MF recurrences as well as one OutF recurrence. CONCLUSION: Target delineation and coverage were adequate. The majority of locoregional failures were InF, i.e., in the high-dose region. Future work on dose escalation to the highest risk regions is recommended.

Randomized clinical trial on reduction of radiotherapy dose to the elective neck in head and neck squamous cell carcinoma; update of the long-term tumor outcome.

BACKGROUND AND PURPOSE: A multicenter prospective randomized controlled trial was performed to investigate whether dose reduction to the elective nodal volume (PTVelect) in head and neck carcinoma reduces radiation-induced dysphagia, primary endpoint, without compromising tumor control, secondary endpoint. Here, we report on the long-term follow-up of the secondary endpoint (NCT01812486). MATERIALS AND METHODS: Two hundred patients treated with primary (chemo)radiotherapy (RT) were randomized (1:1) between the standard arm, irradiation to PTVelect up to an equivalent dose (EQD2) of 50 Gy and the experimental arm, irradiation to PTVelect up to EQD2 of 40 Gy. The primary tumor and involved nodes were treated according to the standard of care, EQD2 70 Gy (PTVhigh). Regional recurrences (RR) were projected on the initial RT planning-CT to identify the recurrence localization. RESULTS: The 5-year (5Y) RR was 14.0% (CI95% 7.9; 21.8) in the 40 Gy arm versus 7.5% (CI95% 3.3; 14.0) in the 50 Gy arm (p = 0.10). Majority of RR in the 40 Gy arm (9/13) were projected in PTVhigh and 2 RR were seen outside the treated RT volume. Only 2 RR occurred in PTVelect irradiated up to 40 Gy which was the same number as RR occurring in the 50 Gy PTVelect. The 5Y-overall survival (OS) was 56.5% (CI95% 45.7; 65.9) in the 40 Gy arm versus 49.6% (CI95% 39.0; 59.2) in the 50 Gy arm (p = 0.56). CONCLUSION: At 5-years, no statistically significant differences regarding OS, local recurrence, RR nor distant metastases were observed between both treatment arms. This study is underpowered to undoubtedly demonstrate non-inferiority. However, since in both arms only two RR in the PTVelect were observed, reducing the dose to PTVelect appears safe and should be further investigated.

Survival benefit with radiation therapy in node-positive breast carcinoma patients.

BACKGROUND AND PURPOSE: Postoperative radiation therapy (RT) has been the subject of discussion, especially in patients with one to three positive lymph nodes (< or = 3 pN+) in the axillary dissection. The authors investigated whether postoperative RT provides a survival benefit for pT1-2 pN+ breast cancer patients. PATIENTS AND METHODS: Patients included were selected from the SEER database (NCI--Surveillance, Epidemiology and End Results, release 2000; n = 24,410) and the UZ Brussel database (1984-2002; n = 1,011) according to the following criteria: women aged 25-95, no previous cancer, unilateral pT1-pT2 breast tumors, total mastectomy (ME) or breast-conserving surgery (BCS), postoperative RT, and an axillary dissection showing at least one pathologic lymph node. RESULTS: The overall survival (OS) of patients in the SEER and UZ Brussel databases who received postoperative RT was identical. However, patients in the SEER database who did not receive RT had a significantly worse outcome (p < 0.0001). After ME or BCS, all patients (SEER and UZ Brussel) who had > or = 4 pN+ and received RT had comparable outcomes after 15 years. The 15-year OS in the subgroup with ME and < or = 3 pN+ nodes was 57.0% and 46.6% (p = 0.0004) with RT (UZ Brussel) and without RT (SEER), respectively. For BCS and < or = 3 pN+, the same significant difference in OS at 15 years was seen: 63.8% after RT (UZ Brussel) and 60.4% without RT (SEER; p = 0.0029). CONCLUSION: RT provides a survival benefit in patients with < or = 3 or > or = 4 pN+; the indication for postoperative RT should therefore be adapted in future consensus meetings.

An assessment of the use of skin flashes in helical tomotherapy using phantom and in-vivo dosimetry.

BACKGROUND AND PURPOSE: In helical tomotherapy the nature of the optimizing and planning systems allows the delivery of dose on the skin using a build-up compensating technique (skin flash). However, positioning errors or changes in the patient's contour can influence the correct dosage in these regions. This work studies the behavior of skin-flash regions using phantom and in-vivo dosimetry. MATERIALS AND METHODS: The dosimetric accuracy of the tomotherapy planning system in skin-flash regions is checked using film and TLD on phantom. Positioning errors are induced and the effect on the skin dose is investigated. Further a volume decrease is simulated using bolus material and the results are compared. RESULTS: Results show that the tomotherapy planning system calculates dose on skin regions within 2 SD using TLD measurements. Film measurements show drops of dose of 2.8% and 26% for, respectively, a 5mm and 10mm mispositioning of the phantom towards air and a dose increase of 9% for a 5mm shift towards tissue. These measurements are confirmed by TLD measurements. A simulated volume reduction shows a similar behavior with a 2.6% and 19.4% drop in dose, measured with TLDs. CONCLUSION: The tomotherapy system allows adequate planning and delivery of dose using skin flashes. However, exact positioning is crucial to deliver the dose at the exact location.

Reduction of the dose of radiotherapy to the elective neck in head and neck squamous cell carcinoma; a randomized clinical trial. Effect on late toxicity and tumor control.

BACKGROUND AND PURPOSE: A multi-center prospective randomized clinical trial has been performed investigating whether a reduction of the dose to the elective nodal sites in head and neck cancer delivered by intensity modulated radiotherapy (IMRT) would result in a reduction of late side effects without compromising tumor control. MATERIALS AND METHODS: Two hundred patients were included. The prescription dose to the elective nodal volumes was a normalized iso-effective dose in 2Gy fractions (NID2Gy) of 50Gy in the standard arm and of 40Gy in the experimental arm. Late toxicity was scored at 6, 12, 18 and 24months using the RTOG scoring system. RESULTS: We observed a trend toward less dysphagia at 6months in the experimental arm, however this was not confirmed after longitudinal analysis. Regarding moderate salivary gland toxicity we observed lower incidence of salivary gland toxicity ⩾grade 1, at 6 (p=0.01) and 18months (p=0.03). After two years of follow up, we did not observe significant differences in estimated local failure rate (14.1% in the 40Gy arm vs 14.4% in the 50Gy arm), estimated regional failure rate (13.0% vs 5.5% in the 40 and the 50Gy arm respectively), estimated metastatic recurrence (13.4% vs 18.5% in the 40 and the 50Gy arm respectively), estimated disease-free survival (57.9% vs 65.3% in the 40 and the 50Gy arm respectively) nor estimated overall survival (72.0% vs 73.2% in the 40 and the 50Gy arm respectively). CONCLUSIONS: In our study population there was no statistically significant difference regarding survival and estimated recurrence rates between both arms of this study. We found a trend toward less dysphagia at 6months (however not significant after longitudinal analysis) and found a significant reduction of any salivary gland toxicity at 6 and 18months in the 40Gy arm.

Modeling the effect of age in T1-2 breast cancer using the SEER database.

BACKGROUND: Modeling the relationship between age and mortality for breast cancer patients may have important prognostic and therapeutic implications. METHODS: Data from 9 registries of the Surveillance, Epidemiology, and End Results Program (SEER) of the United States were used. This study employed proportional hazards to model mortality in women with T1-2 breast cancers. The residuals of the model were used to examine the effect of age on mortality. This procedure was applied to node-negative (N0) and node-positive (N+) patients. All causes mortality and breast cancer specific mortality were evaluated. RESULTS: The relationship between age and mortality is biphasic. For both N0 and N+ patients among the T1-2 group, the analysis suggested two age components. One component is linear and corresponds to a natural increase of mortality with each year of age. The other component is quasi-quadratic and is centered around age 50. This component contributes to an increased risk of mortality as age increases beyond 50. It suggests a hormonally related process: the farther from menopause in either direction, the more prognosis is adversely influenced by the quasi-quadratic component. There is a complex relationship between hormone receptor status and other prognostic factors, like age. CONCLUSION: The present analysis confirms the findings of many epidemiological and clinical trials that the relationship between age and mortality is biphasic. Compared with older patients, young women experience an abnormally high risk of death. Among elderly patients, the risk of death from breast cancer does not decrease with increasing age. These facts are important in the discussion of options for adjuvant treatment with breast cancer patients.

Statistical interaction in the survival analysis of early breast cancer using registry data: role of breast conserving surgery and radiotherapy.

PURPOSE: To identify subgroup effects that might influence the survival results of postoperative radiotherapy. PATIENTS AND METHODS: Women selected from the Surveillance, Epidemiology, and End Results database, aged 40-69 years, with non-metastasized T1-T2 breast carcinoma, in whom axillary lymph node dissection was performed. Subgroup analyses were performed using proportional hazards models with interactions. Joint significance of subgroups was evaluated with the Wald test. Event was death from any cause. RESULTS: Statistically significant interactions were found between type of surgery (breast-conserving [BCS] or mastectomy [ME]), radiotherapy [RT], T stage, and extent of nodal involvement, but not between treatments and nodal examination. For each treatment combination, ME-no RT, ME+RT, BCS-no RT, BCS+RT, the mortality hazard ratios were respectively: 1, 1.12, 1.11, 0.78 in T1, 0-3 positive nodes; 2.45, 2.77, 2.71, 1.92 in T2, 4+ nodes; 1.31, 1.38, 1.33, 1.19 in T2, 0-3+ nodes; and 3.41, 2.79, 3.44, 2.40 in T2, 4+ nodes. The corresponding joint tests showed: in the absence of radiotherapy, no significant survival disadvantage for breast-conserving surgery vs mastectomy; with radiotherapy, significant survival advantage for breast-conserving surgery irrespective of stage and for mastectomy in T2, 4+ nodes. For mastectomy in less advanced stages receiving radiotherapy, excess breast cancer deaths suggested undocumented adverse selection. The corresponding result was considered inconclusive. CONCLUSIONS: The analyses found subgroup effects that should be taken into account to interpret treatment results in breast cancer.

Ratios of involved nodes in early breast cancer.

INTRODUCTION: The number of lymph nodes found to be involved in an axillary dissection is among the most powerful prognostic factors in breast cancer, but it is confounded by the number of lymph nodes that have been examined. We investigate an idea that has surfaced recently in the literature (since 1999), namely that the proportion of node-positive lymph nodes (or a function thereof) is a much better predictor of survival than the number of excised and node-positive lymph nodes, alone or together. METHODS: The data were abstracted from 83,686 cases registered in the Surveillance, Epidemiology, and End Results (SEER) program of women diagnosed with nonmetastatic T1-T2 primary breast carcinoma between 1988 and 1997, in whom axillary node dissection was performed. The end-point was death from breast cancer. Cox models based on different expressions of nodal involvement were compared using the Nagelkerke R2 index (R2N). Ratios were modeled as percentage and as log odds of involved nodes. Log odds were estimated in a way that avoids singularities (zero values) by using the empirical logistic transform. RESULTS: In node-negative cases both the number of nodes excised and the log odds were significant, with hazard ratios of 0.991 (95% confidence interval 0.986-0.997) and 1.150 (1.058-1.249), respectively, but without improving R2N. In node-positive cases the hazard ratios were 1.003-1.088 for the number of involved nodes, 0.966-1.005 for the number of excised nodes, 1.015-1.017 for the percentage, and 1.344-1.381 for the log odds. R2N improved from 0.067 (no nodal covariate) to 0.102 (models based on counts only) and to 0.108 (models based on ratios). DISCUSSION: Ratios are simple optimal predictors, in that they provide at least the same prognostic value as the more traditional staging based on counting of involved nodes, without replacing them with a needlessly complicated alternative. They can be viewed as a per patient standardization in which the number of involved nodes is standardized to the number of nodes excised. In an extension to the study, ratios were validated in a comparison with categorized staging measures using blinded data from the San Jose-Monterey cancer registry. A ratio based prognostic index was also derived. It improved the Nottingham Prognostic Index without compromising on simplicity.

Adjuvant radiotherapy after mastectomy for pT1-pT2 node negative (pN0) breast cancer: is it worth the effort?

PURPOSE: Postoperative radiotherapy (RT) for pT1-2 pN0 breast cancer was the standard treatment in our department. Since little data on the importance of RT in this subgroup are known, we reviewed the clinical records with regard to overall survival. MATERIAL AND METHODS: From 1984 until 2000, 1789 files were submitted to retrospective analyses; 731 had a pT1 (n=427) or pT2 (n=304) pN0 lesion. They were treated with breast conserving surgery (BCS) (n=343) or mastectomy (ME) (n=388), axillary lymph node dissection (ALND) and post-operative RT. The outcome was analyzed and compared with the patients included in the SEER-Data 1988-1997 (NCI-Surveillance, Epidemiology and End Results, release 2000) that were treated according to the standard treatment: BCS+ALND+RT, or ME+ALND no RT. RESULTS: The actuarial overall survival (OS) at 5 and 10 years after BCS was 93.3% and 85.1% for pT1 and 88.3% and 75.4% for pT2 tumors. These results are comparable with the SEER (93.9%, 84.9% for pT1, and 87.3%, 76.7% for pT2, respectively). For our ME patients the OS was 91.8% and 79.9%, respectively (pT1 at 5 and 10 years, respectively), and 83.6% and 70.4% (pT2 at 5 and 10 years). In the SEER data the analyses resulted in 89.3% and 73.8% (pT1), and 81.1% and 63.5% (pT2), respectively. DISCUSSION: Although both databases are retrospective, the comparable survival in BCS patients pleads for the similarity of the two populations. The better OS observed in ME patients treated with RT compared to the SEER patients argues in favor of a benefit due to adjuvant radiotherapy. CONCLUSION: Radiotherapy after mastectomy might improve survival in low-risk node negative patients. Our data shows an absolute benefit of between 2.5% and 6.9% OS in favor of post ME radiotherapy, compared to the SEER data.

Omission of radiotherapy after breast-conserving surgery: survival impact and time trends.

PURPOSE: To evaluate the survival impact of omission of radiotherapy after breast-conserving surgery and the changes with time. MATERIAL AND METHODS: Women aged 40-69 with non-metastasized T1-T2 breast cancer, who underwent breast-conserving surgery with axillary node dissection, with or without post-surgery radiotherapy, selected from the SEER (Surveillance, Epidemiology, and End Results) database. The analysis uses proportional hazards models. RESULTS: Omission of radiotherapy as compared to delivery of radiotherapy was associated with an overall increased mortality hazard ratio of 1.346 (95% confidence interval: 1.204-1.504). Test of constancy showed significant changes with time. The time profile suggested an exponential-like increase from a baseline mortality hazard ratio of 1.17, or 17% excess of relative mortality risk, to a projected hazard ratio of 2.26, or more than doubling of relative mortality risk, for omission of radiotherapy. CONCLUSION: Omission of radiotherapy in breast-conserving surgery is found to be independently associated with an increase in mortality. The data do not give support to omitting radiation or give rationale to clinical trials that would omit radiation.

The lymph node ratio as prognostic factor in node-positive breast cancer.

BACKGROUND AND PURPOSE: The clinical records of the node-positive breast cancer patients treated at our department were reviewed, to evaluate if there is a correlation between the ratio of involved axillary lymph nodes and the overall and cause specific survival. PATIENTS AND METHODS: From 1984 until July 2001, 2073 files from patients with an invasive breast carcinoma were submitted to retrospective analyses. In 810 cases, a node positive status was diagnosed. All pT-stages were included. The total number of dissected nodes (pNtot) and the number of involved nodes (pN+) were available for 741 patients. The ratio of nodal involvement (pN+%) was categorized into three groups, pN+%< or =10% (n = 212) between 11 and 50% (n = 346) and between 51 and 100% (n = 183). RESULTS: The actuarial overall survival (OS) at 5 and 10 years was, respectively, 78.2 and 59.1%. Cause specific survival (CSS) rates were, respectively, 83.6 and 69.1%. In univariate analyses, age (P = 0.01), grade (P = 0.02), pT-stage (P < 0.0001), chemotherapy (P = 0.0002), the number of involved nodes < or =3 versus >3 (pN+) (P < 0.0001) and ratio pN+% (P < 0.0001) were associated significantly with overall survival. A multivariate analysis using the Cox proportional hazards model found that pN+% was the most significant prognostic factor; pN+lost significance when pN+% was taken into account. CONCLUSIONS: The percentage of positive lymph nodes in an axillary lymph node dissection appears to be an important prognostic factor for survival. The nodes ratio improved on the absolute numbers of involved axillary lymph nodes for assessment of prognosis.

Evaluation of dose calculation algorithms for dynamic arc treatments of head and neck tumors.

BACKGROUND AND PURPOSE: To investigate if the Pencil Beam (PB) algorithm takes the disturbance of the dose distribution due to tissue inhomogeneities sufficiently into account in dynamic field shaping rotation therapy (called the dynamic arc treatment modality) for fractionated stereotactic radiation therapy of head and neck tumors. MATERIAL AND METHODS: A treatment plan using the dynamic arc treatment modality of an oropharynx lesion on a humanoid phantom was evaluated. The same plan was calculated with three different calculation algorithms: the Clarkson and the PB algorithm (both available on the planning system of the Novalis system used for dynamic arc treatments), and the Collapsed Cone Convolution Superposition (CC) algorithm (used by the Pinnacle planning system). The three resulting plans are compared using isodose distributions and cumulative dose volume histograms (CDVHs). An intercomparison of the results of the three algorithms was performed to investigate how accurately each of them takes the influence of tissue inhomogeneities into account such as bony structures and air cavities often appearing in the head and neck region. Additionally, the resulting plans were compared with absolute and relative dosimetric measurements of the treatment plan on the humanoid phantom with thermoluminescent detectors and radiographic film, respectively. RESULTS: All calculated dose distributions show a good agreement with the measured distribution except in the planning target volume (PTV) in and at the border of the air cavity. All three algorithms overestimate the dose in the PTV at the boundary with the low-density tissue, with 12, 10 and 7% for the Clarkson, the PB and the CC algorithm, respectively. The correspondence between the calculated dose distributions is reflected in the graphs of the CDVHs. They show similar curves for the PTV and the structures except for the left parotic gland and the myelum. CONCLUSIONS: The PB algorithm of the Novalis system calculates a treatment plan for the dynamic arc treatment modality adequately for fractionated stereotactic radiation therapy of head and neck tumors, except in the PTV in and at the border of the air cavity where the actual dose is overestimated. Care needs to be taken in clinical cases where it is critical to irradiate the air-tissue boundary to a sufficient dose.

Functional form of the effect of the numbers of axillary nodes on survival in early breast cancer.

The change in survival in function of the numbers of involved and uninvolved axillary nodes in early breast cancer - i.e. the functional form - was investigated to search for prognostic cutoffs and to assess if ratio-based characterization of node involvement is a significant prognostic factor or not. Women aged 40-69, diagnosed in 1988-1997 with T1-T2 invasive breast carcinoma, who underwent axillary dissection, are selected from the SEER public database. The method determines the functional form by applying smoothed plots to the martingale residuals obtained from a proportional hazards model. The results on 55,267 selected patients find that the ratio of involved nodes on examined nodes, in a multivariate model that takes into account known prognostic factors (age, race, tumor size, topography, histology, grade, hormone receptors), is associated with a relative mortality hazard of 1.012 (95% confidence interval 1.010-1.014; relative increase of mortality of 1.2% for each 1% increase in the percentage of involved nodes). The functional form for the number of uninvolved nodes shows that the relative mortality hazard initially steeply decreases and then tends to level off beyond 5-10 uninvolved nodes. For the number of involved nodes, the relative mortality hazard continues to increase with each involved node without any obvious cutpoint. Even when the number of involved nodes is already large, each additional involved node increases the relative mortality hazard by at least 1.3%.

Effect of the number of uninvolved nodes on survival in early breast cancer.

A high number of uninvolved axillary nodes was found by some authors to be associated with poor survival in node-negative breast cancer. We searched for confirmation and extend the investigation to node-positive cases, using population data from the SEER Program. Patients selected were women aged 40-69 years, diagnosed 1988-1997, T1-T2 breast cancer, undergoing axillary dissection with 4-35 nodes examined. Survivals were estimated by the product-limit method and were computed on pooled data. Results in node-negative patients (n=37,519) showed a 5-year overall survival from 92% (95% confidence interval: 88-95%) with 4 uninvolved nodes, to 93% (87-98%) with 34 uninvolved nodes. In node-positive patients (n=16,978), the 5-year survival increased from 50% (44-56%) with 0 uninvolved nodes, to 91% (82-100%) with 30 uninvolved nodes. Survival graphs indicated an improvement or a plateau with higher number of uninvolved nodes. The graphs also suggested that the ratio of involved and uninvolved nodes might be correlated with survival. We conclude that there was no evidence of poor outcome associated with a high number of uninvolved nodes. The incidental finding that ratio-based characterization of node involvement might be a prognostic factor will be further investigated.

Reduction of the dose to the elective neck in head and neck squamous cell carcinoma, a randomized clinical trial using intensity modulated radiotherapy (IMRT). Dosimetrical analysis and effect on acute toxicity.

BACKGROUND AND PURPOSE: A randomized trial was initiated to investigate whether a reduction of the dose to the elective nodal sites and the swallowing apparatus delivered by IMRT would result in a reduction of acute and late side effects without compromising tumor control. The aim of this paper is to report on dosimetrical analysis and acute toxicity. MATERIALS & METHODS: Two-hundred patients were randomized. In the standard arm, elective nodal volumes (PTVelect) were irradiated up to an equivalent dose of 50Gy. In the experimental arm an equivalent dose of 40Gy was prescribed to the PTVelect. The dose to the swallowing apparatus was kept as low as possible without compromising therapeutic PTV (PTVther) coverage. RESULTS: No significant difference was seen between both arms concerning PTVther coverage. The median D95 of the PTVelect was significantly lower in the experimental arm (39.5 vs 49.8Gy; p<0.001). Concerning the organs at risk, the dose to swallowing structures and spinal cord was significantly reduced. There was no significant difference in acute toxicity. Three months after radiotherapy there was significantly less grade ⩾3 dysphagia in the experimental arm (2% vs 11%; p=0.03). With a median follow-up of 6months no significant differences were observed in locoregional control, disease free survival or overall survival. CONCLUSIONS: Using IMRT we were able to significantly reduce the dose to the PTVelect and several organs at risk without compromising PTVther coverage. This resulted in a significant reduction of severe dysphagia 3months after radiotherapy. Further follow-up is necessary to investigate whether these observations translate into a benefit on late treatment related dysphagia without affecting treatment outcome.

Parotid gland sparing with helical tomotherapy in head-and-neck cancer.

PURPOSE: This study evaluated the ability of helical tomotherapy to spare the function of the parotid glands in patients with head-and-neck cancer by analyzing dose-volume histograms, salivary gland scintigraphy, and quality of life assessment. METHODS AND MATERIALS: Data from 76 consecutive patients treated with helical tomotherapy (Hi-Art Tomotherapy) at the University Hospital Brussel were analyzed. During planning, priority was given to planning target volume (PTV) coverage: ≥ 95% of the dose must be delivered to ≥ 95% of the PTV. Elective nodal regions received 54 Gy (1.8 Gy/fraction). A dose of 70.5 Gy (2.35 Gy/fraction) was prescribed to the primary tumor and pathologic lymph nodes (simultaneous integrated boost scheme). Objective scoring of salivary excretion was performed by salivary gland scintigraphy. Subjective scoring of salivary gland function was evaluated by the European Organization for Research and Treatment of Cancer quality of life questionnaires Quality of Life Questionnaire-C30 (QLQ-C30) and Quality of Life Questionnaire-Head and Neck 35 (H&N35). RESULTS: Analysis of dose-volume histograms (DVHs) showed excellent coverage of the PTV. The volume of PTV receiving 95% of the prescribed dose (V95%) was 99.4 (range, 96.3-99.9). DVH analysis of parotid gland showed a median value of the mean parotid dose of 32.1 Gy (range, 17.5-70.3 Gy). The median parotid volume receiving a dose <26 Gy was 51.2%. Quality of life evaluation demonstrated an initial deterioration of almost all scales and items in QLQ-C30 and QLQ-H&N35. Most items improved in time, and some reached baseline values 18 months after treatment. CONCLUSION: DVH analysis, scintigraphic evaluation of parotid function, and quality of life assessment of our patient group showed that helical tomotherapy makes it possible to preserve parotid gland function without compromising disease control. We recommend mean parotid doses of <34 Gy and doses <26 Gy to a maximum 47% of the parotid volume as planning goals. Intensity-modulated radiotherapy should be considered as standard treatment in patients with head-and-neck cancer.