Holger Hof

Stereotactic single-dose radiotherapy of stage I non–small-cell lung cancer (NSCLC)

PURPOSE The treatment of early-stage lung cancers is a primary domain of thoracic surgery, leading to persuasive results. In patients with medical contraindications, radiotherapy is an alternative, although with considerably worse outcome. Radiotherapy is associated with the risk of severe acute side effects and a permanent decrease of lung function. By the introduction of an extracranial stereotactic treatment technique, the amount of normal tissue in the high-dose region can be reduced, allowing the performance of single-dose treatment with high, biologically effective doses. METHODS AND MATERIALS Between October 1998 and May 2001, 10 patients with histologically confirmed Stage I non-small-cell lung cancer were treated with stereotactic single-dose radiotherapy. A self-developed stereotactic frame was used for patient positioning and navigation. Total doses applied ranged from 19 to 26 Gy. After treatment, regular CT-based follow-up was performed. RESULTS During a median follow-up period of 14.9 months, the tumors in 8 of 10 patients were locally controlled. The actuarial overall survival was 80% and 64%, respectively, 12 and 24 months after therapy. Actuarial local recurrence-free survival reached 88.9% and 71.1%, respectively. Therapy-related perifocal normal-tissue reaction occurred in 70% of all treated patients, although no major clinical symptoms were seen. In 5 patients, systemic metastases were found during follow-up; 1 patient developed suspect mediastinal lymph nodes. CONCLUSION Stereotactic single-fraction radiotherapy is a feasible, safe, and effective procedure for the treatment of Stage I non-small-cell lung cancer. It promises high local control with a reduced overall treatment time. However, further investigation in a larger patient collective with extended follow-up is necessary.

Stereotactic radiosurgery (SRS): treatment option for recurrent glioblastoma multiforme (GBM).

This article describes the results of a study of stereotactic radiosurgery (SRS) in the treatment of patients with recurrent malignant glioma.

Evaluation of salivary gland function after treatment of head-and-neck tumors with intensity-modulated radiotherapy by quantitative pertechnetate scintigraphy

PURPOSE To evaluate salivary gland function after inversely planned stereotactic intensity-modulated radiotherapy (IMRT) for tumors of the head-and-neck region using quantitative pertechnetate scintigraphy. METHODS AND MATERIALS Since January 2000, 18 patients undergoing IMRT for cancer of the head and neck underwent pre- and posttherapeutic scintigraphy to examine salivary gland function. The mean dose to the primary planning target volume was 61.5 Gy (range 50.4-73.2), and the median follow-up was 23 months. In all cases, the parotid glands were directly adjacent to the planning target volume. The treatment planning goal was for at least one parotid gland to receive a mean dose of <26 Gy. Two quantitative parameters (change in maximal uptake and change in the relative excretion rate before and after IMRT) characterizing the change in salivary gland function after radiotherapy were determined. These parameters were compared with respect to the dose thresholds of 26 and 30 Gy for the mean dose. In addition, dose-response curves were calculated. RESULTS Using IMRT, it was possible in 16 patients to reduce the dose for at least one parotid gland to < or =26 Gy. In 7 patients, protection of both parotid glands was possible. No recurrent disease adjacent to the protected parotid glands was observed. Using the Radiation Therapy Oncology Group/European Organization for the Research and Treatment of Cancer scoring system, only 3 patients had Grade 2 xerostomia. No greater toxicity was seen for the salivary glands. The change in the relative excretion rate was significantly greater, if the parotid glands received a mean dose of > or =26 Gy or > or =30 Gy. For the change in maximal uptake, a statistically significant difference was seen only for the parotid glands and a dose threshold of 30 Gy. For the end point of a reduction in the parotid excretion rate of >50% and 75%, the dose-response curves yielded a dose at 50% complication probability of 34.8 +/- 3.6 and 40.8 +/- 5.3 Gy, respectively. CONCLUSION Using IMRT, it is possible to protect the parotid glands and reduce the incidence and severity of xerostomia in patients. Doses <26-30 Gy significantly preserve salivary gland function. The results support the hypothesis that application of IMRT does not lead to increased local failure rates.

ASSESSMENT OF FOCAL LIVER REACTION BY MULTIPHASIC CT AFTER STEREOTACTIC SINGLE-DOSE RADIOTHERAPY OF LIVER TUMORS

PURPOSE To characterize and quantitatively assess focal radiation reactions in the liver after stereotactic single-dose radiotherapy for liver malignancies. METHODS AND MATERIALS A total of 131 multiphasic CT scans were performed in 36 patients before and after stereotactic radiotherapy for liver tumors. The examination protocol included a nonenhanced scan and contrast-enhanced scans at different times after contrast injection. The volume of the reaction was determined in each scan and the threshold dose calculated using the dose-volume histogram of the treatment plan. RESULTS Every patient showed a focal radiation reaction on at least one follow-up examination. In 74% of the posttherapeutic scans, a sharply demarcated hypodense area surrounded the treated tumor in the nonenhanced scans. The reaction occurred at a median of 1.8 months (range 1.2-4.6) after radiotherapy. The median threshold dose was 13.7 Gy (range 8.9-19.2). The threshold dose strongly correlated with the time of detection after therapy (r = 0.7). Radiologically, three reaction types were found on the enhanced scans: type 1, portal-venous phase: hypodense and late phase: isodense; type 2, portal-venous phase: hypodense and late phase: hyperdense; and type 3, portal-venous phase: isodense/hyperdense and late phase: hyperdense. Type 1 or 2 reactions were observed significantly earlier than type 3 (p <0.05). The median threshold dose for type 1 or 2 reactions was significantly lower than for type 3 (p <0.05). The reaction volume decreased with longer follow-up (2-4 months: median 40% of initial volume). The reaction types shifted with follow-up: 58% were of type 1 at the initial manifestation and 58% were of type 3 at the next examination thereafter. CONCLUSION A focal radiation reaction occurs after stereotactic single-dose therapy in the liver. The volume of the reaction decreases and changes its radiologic appearance during follow-up. This reaction has to be differentiated from recurrent tumor.

Stereotactic single-dose radiotherapy (radiosurgery) of early stage nonsmall-cell lung cancer (NSCLC).

The clinical results after stereotactic single‐dose radiotherapy of nonsmall‐cell lung cancer (NSCLC) stages I and II were evaluated.

Effectiveness of cetuximab/gefitinib in the therapy of a sacral chordoma

Background: Chordomas are rare tumors of the skull base and the spine. Treatment is difficult since conventional radiotherapy or chemotherapy have only limited effects. Patient and Methods: A patient with a sacral chordoma and pulmonary metastases received initial surgery and radiotherapy for a local recurrence. After 11 months another local recurrence as well as a progression of the pulmonary metastases was documented. As tumor biopsies revealed the expression of the EGF receptor an individual treatment approach with a combination of cetuximab and gefitinib was performed. Results: Under the treatment with cetuximab/gefitinib the local recurrence and the pulmonary metastases showed a partial response over the follow-up period of 9 months. To date no treatment failure was observed. Conclusions: The inhibition of the EGF pathway seems to be an effective measure in the treatment of a chordoma. Further follow- up will have to prove the long-term efficiency.

Stereotactic single-dose radiotherapy of lung metastases.

Background:Stereotactic treatment approaches lead to a significant reduction of irradiated volumes, which should make pulmonary targets more accessible to radiotherapy.Patients and Methods:Between May 1997 and December 2005, 61 patients received stereotactic single-dose dose treatment for 71 pulmonary metastases. Doses to the isocenter ranged from 12 to 30 Gy. Survival and local tumor control rates were evaluated prospectively.Results:After a median follow-up period of 14 months the actuarial overall survival was 78.4%, 65.1%, and 47.8% 12, 24, and 36 months after therapy, respectively. There was a significantly better survival (p = 0.023) for patients not developing further metastases during follow-up. The actuarial local progression-free rate was 88.6%, 73.7%, and 63.1% 12, 24, and 36 months after therapy. Although the majority of patients (70.4%) developed perifocal normal-tissue changes, these were not related to clinically relevant toxicities.Conclusion:Stereotactic single-dose radiotherapy is a feasible, safe and effective local treatment option for solitary pulmonary metastases in patients with contraindications to surgery or for palliation of symptomatic pulmonary metastases.Hintergrund:Stereotaktische Bestrahlungsansätze führen zu einer signifikanten Reduktion der bestrahlten Volumina, was intrapulmonale Zielstrukturen der Strahlentherapie zugänglicher machen sollte.Patienten und Methodik:Zwischen Mai 1995 und Dezember 2005 erhielten 61 Patienten eine stereotaktische Einzeitbestrahlung von 71 Lungenmetastasen (Tabelle 1) unter Verwendung von Strahlendosen von 12–30 Gy (Tabellen 1 und 2). Überleben und lokale Tumorkontrollraten wurden prospektiv evaluiert.Ergebnisse:Nach einer medianen Nachbeobachtungszeit von 14 Monaten betrug das aktuarische Gesamtüberleben 12, 24 und 36 Monate nach Therapie 78,4%, 65,1% und 47,8% (Abbildung 1). Das Überleben war bei Patienten, welche keine weiteren Metastasen während der Nachbeobachtung entwickelten, signifikant verlängert (Abbildung 2). Die aktuarische lokale Progressionsfreiheit betrug 12, 24 und 36 Monate nach Therapie 88,6%, 73,7% und 63,1% (Abbildungen 3 und 4). Obwohl die Mehrzahl der Patienten (70,4%) perifokale Normalgewebsveränderungen entwickelte, korrelierten diese nicht mit klinisch relevanten Toxizitäten (Tabelle 3).Schlussfolgerung:Die stereotaktische Einzeitbestrahlung ist eine praktikable, sichere und effektive lokale Behandlungsoption für solitäre Lungenmetastasen bei Patienten mit Kontraindikationen für eine Operation oder zur Palliation symptomatischer Lungenmetastasen.

Neoadjuvant chemoradiation with Gemcitabine for locally advanced pancreatic cancer

IntroductionTo evaluate efficacy and secondary resectability in patients with locally advanced pancreatic cancer (LAPC) treated with neoadjuvant chemoradiotherapy (CRT).Patients and methodsA total of 215 patients with locally advanced pancreatic cancer were treated with chemoradiation at a single institution. Radiotherapy was delivered with a median dose of 52.2 Gy in single fractions of 1.8 Gy. Chemotherapy was applied concomitantly as gemcitabine (GEM) at a dose of 300 mg/m2 weekly, followed by adjuvant cycles of full-dose GEM (1000 mg/m2). After neoadjuvant CRT restaging was done to evaluate secondary resectability. Overall and disease-free survival were calculated and prognostic factors were estimated.ResultsAfter CRT a total of 26% of all patients with primary unresectable LAPC were chosen to undergo secondary resection. Tumour free resection margins could be achieved in 39.2% (R0-resection), R1-resections were seen in 41.2%, residual macroscopic tumour in 11.8% (R2) and in 7.8% resection were classified as Rx. Patients with complete resection after CRT showed a significantly increased median overall survival (OS) with 22.1 compared to 11.9 months in non-resected patients. Median OS and disease-free survival (DFS) of all patients were 12.3 and 8.1 months respectively. In most cases the first site of disease progression was systemic with hepatic (52%) and peritoneal (36%) metastases.DiscussionA high percentage of patients with locally advanced pancreatic cancer can undergo secondary resection after gemcitabine-based chemoradiation and has a relative long-term prognosis after complete resection.

4D-CT-based target volume definition in stereotactic radiotherapy of lung tumours: Comparison with a conventional technique using individual margins

PURPOSE To investigate the dosimetric benefit of integration of 4D-CT in the planning target volume (PTV) definition process compared to conventional PTV definition using individual margins in stereotactic body radiotherapy (SBRT) of lung tumours. MATERIAL AND METHODS Two different PTVs were defined: PTV(conv) consisting of the helical-CT-based clinical target volume (CTV) enlarged isotropically for each spatial direction by the individually measured amount of motion in the 4D-CT, and PTV(4D) encompassing the CTVs defined in the 4D-CT phases displaying the extremes of the tumour position. Tumour motion as well as volumetric and dosimetric differences and relations of both PTVs were evaluated. RESULTS Volumetric examinations revealed a significant reduction of the mean PTV by 4D-CT from 57.7 to 40.7 cm(3) (31%) (p<0.001). A significant inverse correlation was found for the motion vector and the amount of inclusion of PTV(4D) in PTV(conv) (r=-0.69, 90% confidence limits: -0.87 and -0.34, p=0.007). Mean lung dose (MLD) was decreased significantly by 17% (p<0.001). CONCLUSIONS In SBRT of lung tumours the mere use of individual margins for target volume definition cannot compensate for the additional effects that the implementation of 4D-CT phases can offer.

The use of the multislice CT for the determination of respiratory lung tumor movement in stereotactic single-dose irradiation.

Background: In three-dimensional (3-D) precision high-dose radiation therapy of lung tumors, the exact definition of the planning target volume (PTV) is indispensable. Therefore, the feasibility of a 3-D determination of respiratory lung tumor movements by the use of a multislice CT scanner was investigated. Patients and Methods: The respiratory motion of 21 lung tumors in 20 consecutively treated patients was examined. An abdominal pressure device for the reduction of respiratory movement was used in 14 patients. Two regions of the tumor were each scanned repeatedly at the same table position, showing four simultaneously acquired slices for each cycle. Stereotactic coordinates were determined for one anatomic reference point in each tumor region (Figure 1). The 3-D differences of these coordinates between the sequentially obtained cycles were assessed (Figure 2), and a correlation with the tumor localization was performed. Results: In the craniocaudal (Z-)direction the mean tumor movement was 5.1 mm (standard deviation [SD] 2.4 mm, maximum 10 mm), in the ventrodorsal (Y-)direction 3.1 mm (SD 1.5 mm, maximum 6.7 mm), and in the lateral (X-)direction 2.6 mm (SD 1.4 mm, maximum 5.8 mm; Figures 3 to 5). Inter- and intraindividual differences were present in each direction. With an abdominal pressure device no clinically significant difference between tumors in different locations was seen. Conclusion: The 3-D assessment of lung tumor movements due to breathing is possible by the use of multislice CT. The determination, indispensable to the PTV definition, should be performed individually for several regions, because of the inter- and intraindividual deviations detected.Hintergrund: Die dreidimensionale Hochdosispräzisionsbestrahlung von Lungentumoren erfordert eine exakte Definition des Planungszielvolumens (PTV). Daher wurde die Möglichkeit des Einsatzes eines Mehrzeilen-CT-Geräts zur dreidimensionalen Bestimmung der Tumorbewegung in der Lunge untersucht. Patienten und Methodik: In 20 konsekutiv behandelten Patienten wurde die atembedingte Bewegung von 21 Tumoren untersucht. Eine Abdominalkompression zur Minimierung der Atembewegung kam bei 14 Patienten zum Einsatz. Zwei unterschiedliche Tumorregionen wurden jeweils wiederholt ohne Tischvorschub in einer Auflösung von vier simultan akquirierten Schichten über eine Distanz von 1 cm gescannt (sechs Wiederholungen, Scanzeit 0,75 s, Abstand 3 s, Schichtdicke 2,5 mm). Ein anatomischer Referenzpunkt in beiden Tumorregionen wurde festgelegt, und stereotaktische Koordinaten dieses Punkts wurden in jeder Wiederholung bestimmt (Abbildung 1). Die maximale Differenz dieser Koordinaten wurde in allen drei Raumrichtungen berechnet (Abbildung 2) und mit der Tumorlokalisation korreliert. Ergebnisse: Die mittlere Bewegung betrug in kraniokaudaler Richtung 5,1 mm (Standardabweichung [SD] 2,4 mm, Maximum 10 mm), in ventrodorsaler 3,5 mm (SD 1,5 mm, Maximum 6,7 mm) und in mediolateraler Richtung 2,6 mm (SD 1,4 mm, Maximum 5,8 mm; Abbildungen 3 bis 5). In jeder Raumrichtung gab es inter- und intraindividuelle Unterschiede. Unter Verwendung der Abdominalkompression war kein signifikanter Einfluss der Tumorlokalisation auf die Atembeweglichkeit nachzuweisen. Schlussfolgerung: Der Einsatz der Mehrzeilen-CT für die dreidimensionale Bestimmung von atembedingten Lungentumorbewegungen ist möglich. Die zur Definition des PTV notwendige Bestimmung sollte aufgrund der nachgewiesenen inter- und intraindividuellen Unterschiede individuell in mehreren Tumorregionen erfolgen.