Mia Voordeckers

Ratios of involved nodes in early breast cancer

IntroductionThe 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.MethodsThe 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.ResultsIn 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).DiscussionRatios 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.

Longitudinal Assessment of Parotid Function in Patients Receiving Tomotherapy for Head-and-Neck Cancer

Background and Purpose:Conventional radiotherapy is associated with high doses to the salivary glands which causes xerostomia and adverse effects on quality of life. The study aims to investigate the potential of helical tomotherapy (Hi-Art Tomotherapy®) to preserve parotid function in head-and-neck cancer patients.Patients and Methods:Seven consecutive patients treated with helical tomotherapy at the UZ Brussel, Belgium, were included. During planning, priority was attributed 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. If possible, the mean parotid dose was kept below 26 Gy. Salivary gland function was assessed by technetium scintigraphy.Results:There was a significant dose-response relationship between mean parotid dose and functional recuperation. If the mean dose was kept < 31 Gy, a recuperation of 75% can be expected at 12 months. The authors equally observed a significant correlation between salivary excretion (SE) and the percentage of parotid gland receiving a dose < 26 Gy (V26%). In order to preserve 75% of SE, 46% of the parotid volume should receive a dose < 26 Gy.Conclusion:With the use of helical tomography the parotid gland function can largely be preserved since the mean dose to the entire gland as well as glandular volume receiving > 26 Gy can be reduced.Hintergrund und Ziel:Die konventionelle Strahlentherapie zur Behandlung von Kopf-Hals-Tumoren steht häufig im Zusammenhang mit hohen Dosisbelastungen der Speicheldrüsen. Dies verursacht Xerostomie, welche eine Beeinträchtigung der Lebensqualität zur Folge hat. Das Ziel dieser Studie ist die Untersuchung eines möglichen Vorteils helikaler Tomotherapie für die Funktionserhaltung der Ohrspeicheldrüsen.Patienten und Methodik:Eingeschlossen wurden sieben aufeinanderfolgende Patienten mit einer Nachbeobachtungszeit von 12 Monaten, die am Universitätsklinikum Brüssel (UZ Brussel), Belgien, eine helikale Tomotherapie (Hi-Art Tomotherapy®) erhielten. Bei der Planung wurde der Abdeckung des Planungszielvolumens (PTV) höchste Priorität zuerkannt: ≥ 95% des PTV mussten ≥ 95% der Dosis erhalten. Elektive Lymphabstromgebiete erhielten 54 Gy (1,8 Gy/Fraktion). Die Zielvolumendosis im Primärtumor und in pathologischen Lymphknoten betrug 70,5 Gy (2,35 Gy/Fraktion) = simultaner integrierter Boost. Nach Möglichkeit wurde die mittlere Dosis der Parotiden auf 26 Gy beschränkt. Die Funktion der Speicheldrüsen wurde durch Technetium-Szintigraphie ermittelt.Ergebnisse:Es fand sich eine signifikante Dosis-Wirkungs-Beziehung zwischen der mittleren Dosis in der Parotis und der Wiederherstellung ihrer Funktion. Bei einer mittleren Dosis < 31 Gy kann mit einer 75%igen Wiederherstellung innerhalb von 12 Monaten gerechnet werden. Die Autoren beobachteten eine signifikante Korrelation zwischen Speichelfluss (SF) und prozentualem Anteil der Parotis, der eine Dosis < 26 Gy erhielt (V26%). Um 75% des SF zu erhalten, sollten 46% des Parotisvolumens eine Dosis < 26 Gy erhalten.Schlussfolgerung:Die Möglichkeit, mittels helikaler Tomotherapie die Funktion der Speicheldrüsen zu erhalten, hängt nicht nur von der applizierten mittleren Dosis, sondern auch vom prozentualen Anteil des Volumens ab, das < 26 Gy erhält.

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

BackgroundModeling the relationship between age and mortality for breast cancer patients may have important prognostic and therapeutic implications.MethodsData 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.ResultsThe 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.ConclusionThe 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.

Can 18-FDG-PET during radiotherapy replace post-therapy scanning for detection/demonstration of tumor response in head-and-neck cancer?

PURPOSE In routine practice, the tumor response in head-and-neck cancer (HNC) is assessed 3-4 months after radiotherapy (RT). We compared the results of fluorodeoxyglucose-positron emission tomography (FDG-PET) during (47 Gy) and 4 months after RT. METHODS AND MATERIALS In 40 patients with HNC, PET was performed before (PET1), at the end of Week 4 (47 Gy) (PET2), and 4 months after RT (PET3). Visual analysis classified patients as having a complete response (CR) or a non-CR (NCR). The sensitivity, specificity, accuracy, negative predictive value, and positive predictive value for PET2 and PET3 were determined. The 2-year overall survival (OS) rate for a CR and NCR was calculated for both response evaluation points. RESULTS After a median follow-up of 26 months, 10 patients had died, 6 had residual disease, and 24 remained disease free. The overall sensitivity, specificity, negative predictive value, positive predictive value, and accuracy of PET2 vs. PET3 for the detection of a CR was 28.6%, 81.8%, 31.0%, 80.0%, and 42.5% vs. 78.6%, 75.0%, 60.0%, 88.0%, and 77.5%, respectively. The 2-year OS rate determined at 47 Gy was 90.0% and 71.8% for a CR and NCR, respectively, and did not appear to be significantly different (p = .50). For the study, at 4 months, the OS was significantly better in the CR group (91.8%) than in the NCR group (49.9%; p = .0055). CONCLUSION The high specificity and positive predictive value for the evaluation of tumor response with PET2 and PET3 might avoid unnecessary salvage surgery in patients with a CR. In contrast to PET3, the sensitivity of PET 2 was low, and the difference in OS between the CR and NCR groups was not significantly different. Therefore, the evaluation of the tumor response with FDG-PET at 4 months after RT completion cannot be replaced by FDG-PET during RT at 47 Gy.

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.

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.

Can 18F-FDG-PET response during radiotherapy be used as a predictive factor for the outcome of head and neck cancer patients?

ObjectivesWe investigated if (18F) fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG-PET) during radiotherapy or concurrent chemoradiotherapy adds information about the treatment outcome compared with an 18FDG-PET study before treatment. MethodsForty-three patients with head and neck cancer were treated with helical tomotherapy. 18F-FDG-PET was performed at baseline and during the treatment after 47 Gy. Tracer accumulation at the tumor site was assessed visually and semiquantitatively using the maximal standardized uptake values (SUVmax). With median SUVmax of both the studies as cutoff, patients were categorized into low and high SUVmax groups. For visual analysis, two independent observers classified patients as complete metabolic responders (CMR) or noncomplete metabolic responders (NCMR). ResultsAt baseline the median SUVmax was 8.11 (2.41–15.13). The overall survival (OS) and disease-free survival (DFS) were 81 and 67% versus 50 and 40% for the low and high SUVmax, respectively. OS was significantly different (P=0.027). During therapy, median SUVmax was 4.03 (1.94–7.58). OS and DFS were 82 and 63%, versus 47 and 42% for the low and high SUVmax group, respectively. OS was significantly different (P=0.026). No significant differences between CMR versus NCMR in OS (72 vs. 60%), and DFS (56 vs. 49%) were found. ConclusionCategorizing patients on the basis of a semiquantitative approach resulted in significant differences in OS for both the scans before and during therapy. Future work on a larger number of patients is warranted to determine SUVmax cutoff values which could be used for the early identification of patients with poor treatment outcome or perhaps other therapeutic approaches.

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.

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.ZusammenfassungHintergrund und Ziel:Bei der helikalen Tomotherapie (HT, Hi-Art TomoTherapy®) handelt es sich um ein neuartiges Bestrahlungsgerat, welches mit Hilfe einer rotierenden Gantry hochkonformale Dosisverteilungen erreicht. Dies fuhrt zu gleich - masigerer Abdeckung des Zielvolumens und besserer Schonung von Risikoorganen. Ruckfallmuster bei Patienten mit Tumoren in der Kopf-Hals-Gegend (HNC), die mit HT behandelt worden waren, wurden analysiert.Patienten und Methodik:63 Patienten mit bioptisch bewiesenen HNC wurden mit HT behandelt. Bei Patienten mit lokoregionalem Rezidiv wurde das Rezidivvolumen („volume of failure“ [Vf]) eingezeichnet und mit dem ursprunglichen Planungscomputertomogramm verglichen. Mit Hilfe der Analyse von Dosis-Volumen-Histogrammen (DVHs) wurde das Vf eingeteilt in „in-field“ (InF; innerhalb des ursprunglichen Zielvolumens), „marginal“ (MF, Randrezidiv) oder „outside-field“ (OutF, auserhalb des ursprunglichen Zielvolumens), wenn sich jeweils ≥ 95%, 20–94% oder < 20% des Vf innerhalb der 95%-Isodose befanden.Ergebnisse:Die mediane Nachbeobachtungszeit betrug 25 Monate (95%-Konfidenzintervall 19,4–28 Monate). Die 2-Jahres- Uberlebensrate, das krankheitsfreie Uberleben und die lokoregionale Kontrollrate betrugen 66%, 54% und 77%. 13 Patienten entwickelten ein lokoregionales Rezidiv. Nach DVH-Analyse handelte es sich um zehn InF- und zwei MF-Rezidive sowie ein OutF-Rezidiv.Schlussfolgerung:Zielvolumendefinition und -abdeckung waren ausreichend. Der groste Teil der lokoregionalen Rezidive waren InF, d. h. im Hochdosisbereich. Weitere Studien uber Dosiseskalationen in Regionen mit hohem Rezidivrisiko werden empfohlen.

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.