A Dynamic Programming Approach to Adaptive Fractionation

We conduct a theoretical study of various solution methods for the adaptive fractionation problem. The two messages of this paper are: (i) dynamic programming (DP) is a useful framework for adaptive radiation therapy, particularly adaptive fractionation, because it allows us to assess how close to optimal different methods are, and (ii) heuristic methods proposed in this paper are near-optimal, and therefore, can be used to evaluate the best possible benefit of using an adaptive fraction size. The essence of adaptive fractionation is to increase the fraction size when the tumor and organ-at-risk (OAR) are far apart (a "favorable" anatomy) and to decrease the fraction size when they are close together. Given that a fixed prescribed dose must be delivered to the tumor over the course of the treatment, such an approach results in a lower cumulative dose to the OAR when compared to that resulting from standard fractionation. We first establish a benchmark by using the DP algorithm to solve the problem exactly. In this case, we characterize the structure of an optimal policy, which provides guidance for our choice of heuristics. We develop two intuitive, numerically near-optimal heuristic policies, which could be used for more complex, high-dimensional problems. Furthermore, one of the heuristics requires only a statistic of the motion probability distribution, making it a reasonable method for use in a realistic setting. Numerically, we find that the amount of decrease in dose to the OAR can vary significantly (5 - 85%) depending on the amount of motion in the anatomy, the number of fractions, and the range of fraction sizes allowed. In general, the decrease in dose to the OAR is more pronounced when: (i) we have a high probability of large tumor-OAR distances, (ii) we use many fractions (as in a hyper-fractionated setting), and (iii) we allow large daily fraction size deviations.Comment: 17 pages, 4 figures, 1 tabl

Substantial Dose-response Relationship with Clinical Outcome for Lung Stereotactic Body Radiotherapy (SBRT) Delivered via Online Image Guidance

Purpose: To examine potential tumor dose-response relationships with various non-small cell lung cancer (NSCLC) SBRT fractionation regimens delivered with online CT-based image guidance. American Society for Therapeutic Radiation Oncology (ASTRO) 52nd Annual Meeting October 31 - November 4, San Diego, C

Variability in spine radiosurgery treatment planning - results of an international multi-institutional study

Background: The aim of this study was to quantify the variability in spinal radiosurgery (SRS) planning practices between five international institutions, all member of the Elekta Spine Radiosurgery Research Consortium. Methods: Four institutions provided one representative patient case each consisting of the medical history, CT and MR imaging. A step-wise planning approach was used where, after each planning step a consensus was generated that formed the basis for the next planning step. This allowed independent analysis of all planning steps of CT-MR image registration, GTV definition, CTV definition, PTV definition and SRS treatment planning. In addition, each institution generated one additional SRS plan for each case based on intra-institutional image registration and contouring, independent of consensus results. Results: Averaged over the four cases, image registration variability ranged between translational 1.1 mm and 2.4 mm and rotational 1.1° and 2.0° in all three directions. GTV delineation variability was 1.5 mm in axial and 1.6 mm in longitudinal direction averaged for the four cases. CTV delineation variability was 0.8 mm in axial and 1.2 mm in longitudinal direction. CTV-to-PTV margins ranged between 0 mm and 2 mm according to institutional protocol. Delineation variability was 1 mm in axial directions for the spinal cord. Average PTV coverage for a single fraction18 Gy prescription was 87 ± 5 %; Dmin to the PTV was 7.5 ± 1.8 Gy averaged over all cases and institutions. Average Dmax to the PRV_SC (spinal cord + 1 mm) was 10.5 ± 1.6 Gy and the average Paddick conformity index was 0.69 ± 0.06. Conclusions: Results of this study reflect the variability in current practice of spine radiosurgery in large and highly experienced academic centers. Despite close methodical agreement in the daily workflow, clinically significant variability in all steps of the treatment planning process was demonstrated. This may translate into differences in patient clinical outcome and highlights the need for consensus and established delineation and planning criteria

Does Intensity Modulated Radiation Therapy (IMRT) prevent additional toxicity of treating the pelvic lymph nodes compared to treatment of the prostate only?

<p>Abstract</p> <p>Background</p> <p>To evaluate the risk of rectal, bladder and small bowel toxicity in intensity modulated radiation therapy (IMRT) of the prostate only compared to additional irradiation of the pelvic lymphatic region.</p> <p>Methods</p> <p>For ten patients with localized prostate cancer, IMRT plans with a simultaneous integrated boost (SIB) were generated for treatment of the prostate only (plan-PO) and for additional treatment of the pelvic lymph nodes (plan-WP). In plan-PO, doses of 60 Gy and 74 Gy (33 fractions) were prescribed to the seminal vesicles and to the prostate, respectively. Three plans-WP were generated with prescription doses of 46 Gy, 50.4 Gy and 54 Gy to the pelvic target volume; doses to the prostate and seminal vesicles were identical to plan-PO. The risk of rectal, bladder and small bowel toxicity was estimated based on NTCP calculations.</p> <p>Results</p> <p>Doses to the prostate were not significantly different between plan-PO and plan-WP and doses to the pelvic lymph nodes were as planned. Plan-WP resulted in increased doses to the rectum in the low-dose region ≤ 30 Gy, only, no difference was observed in the mid and high-dose region. Normal tissue complication probability (NTCP) for late rectal toxicity ranged between 5% and 8% with no significant difference between plan-PO and plan-WP. NTCP for late bladder toxicity was less than 1% for both plan-PO and plan-WP. The risk of small bowel toxicity was moderately increased for plan-WP.</p> <p>Discussion</p> <p>This retrospective planning study predicted similar risks of rectal, bladder and small bowel toxicity for IMRT treatment of the prostate only and for additional treatment of the pelvic lymph nodes.</p

Aktuelle interdisziplinäre Behandlung von Knochenmetastasen

Eine Vielzahl an Krebspatienten entwickelt im Verlauf Knochenmetastasen. Die daraus folgenden Symptome wie Schmerzen, Funktionsverlust sowie neurologische Symptome können rasch zu einem onkologischen oder auch chirurgischen Notfall werden, es besteht in vielen Fällen rascher Handlungsbedarf. Ziel dieser Arbeit ist die Darstellung der aktuellen, evidenzbasierten interdisziplinären Behandlung von Knochenmetastasen. Grundsätzlich ist die interdisziplinäre Zusammenarbeit und die Abstimmung aller Disziplinen der Goldstandard zur optimalen Behandlung ossärer Metastasen

Distinct effects of rectum delineation methods in 3D-confromal vs. IMRT treatment planning of prostate cancer

BACKGROUND: The dose distribution to the rectum, delineated as solid organ, rectal wall and rectal surface, in 3D conformal (3D-CRT) and intensity-modulated radiotherapy treatment (IMRT) planning for localized prostate cancer was evaluated. MATERIALS AND METHODS: In a retrospective planning study 3-field, 4-field and IMRT treatment plans were analyzed for ten patients with localized prostate cancer. The dose to the rectum was evaluated based on dose-volume histograms of 1) the entire rectal volume (DVH) 2) manually delineated rectal wall (DWH) 3) rectal wall with 3 mm wall thickness (DWH(3)) 4) and the rectal surface (DSH). The influence of the rectal filling and of the seminal vesicles' anatomy on these dose parameters was investigated. A literature review of the dose-volume relationship for late rectal toxicity was conducted. RESULTS: In 3D-CRT (3-field and 4-field) the dose parameters differed most in the mid-dose region: the DWH showed significantly lower doses to the rectum (8.7% ± 4.2%) compared to the DWH(3 )and the DSH. In IMRT the differences between dose parameters were larger in comparison with 3D-CRT. Differences were statistically significant between DVH and all other dose parameters and between DWH and DSH. Mean doses were increased by 23.6% ± 8.7% in the DSH compared to the DVH in the mid-dose region. Furthermore, both the rectal filling and the anatomy of the seminal vesicles influenced the relationship between the dose parameters: a significant correlation of the difference between DVH and DWH and the rectal volume was seen in IMRT treatment. DISCUSSION: The method of delineating the rectum significantly influenced the dose representation in the dose-volume histogram. This effect was pronounced in IMRT treatment planning compared to 3D-CRT. For integration of dose-volume parameters from the literature into clinical practice these results have to be considered

Incidence and survival of patients with oligometastatic esophagogastric cancer: A multicenter cohort study

urpose/objective: This multicenter study assessed the incidence and survival of patients with esophagogastric cancer and oligometastatic disease (OMD) in two tertiary referral cancer centers in The Netherlands and Switzerland. Materials/methods: Between 2010 and 2021, patients with metastatic esophagogastric cancer were identified. Patients with de-novo OMD were included (first-time diagnosis of ≤5 distant metastases on 18F-FDG-PET/CT). Control of the primary tumor was considered in patients who underwent primary tumor resection or definitive chemoradiotherapy without locoregional recurrence. Treatment of OMD was categorized into (1) systemic therapy, (2) local treatment (stereotactic body radiotherapy or metastasectomy), (3) local plus systemic therapy, or (4) best supportive care. The primary outcomes were overall survival (OS) and independent prognostic factors for OS. Independent prognostic factors for OS were analyzed using multivariable Cox proportional hazard models. Results: In total, 830 patients with metastatic esophagogastric cancer were identified of whom 200 patients with de-novo OMD were included (24%). The majority of included patients had esophageal cancer (73%) with adenocarcinoma histology (79%) and metachronous OMD (52%). The primary tumor was controlled in 68%. Treatment of OMD was systemic therapy (25%), local treatment (43%), local plus systemic therapy (13%), or best supportive care (18%). Median follow-up was 14 months (interquartile range: 7-27). Median OS was 16 months (95% CI: 13-21). Improved OS was independently associated with local plus systemic therapy compared with systemic therapy alone (hazard ratio [HR] 0.47, 95% confidence interval [CI]: 0.25-0.87). Worse OS was independently associated with squamous cell carcinoma (HR 1.70, 95% CI: 1.07-2.74), bone oligometastases (HR 2.44, 95% CI: 1.28-4.68), brain oligometastases (HR 1.98, 95% CI: 1.05-4.69), and two metastatic locations (HR 2.07, 95% CI: 1.04-4.12). Median OS after local plus systemic therapy was 35 months (95% CI: 22-NA) as compared with 13 months (95% CI: 9-21, p < 0.001) after systemic therapy alone for OMD. Conclusion: Patients with metastatic esophagogastric cancer present in 25% with de-novo OMD. Local treatment of OMD plus systemic therapy was independently associated with long-term OS and independently improved OS when compared with systemic therapy alone. Randomized controlled trials are warranted to confirm these results. Keywords: Esophageal neoplasms; Gastric neoplasms; Lymphatic metastasis; Metastasectomy; Neoplasm metastasis; Radiosurgery

Corrigendum to 'Long-term outcomes of operable stage III NSCLC in the pre-immunotherapy era: results from a pooled analysis of the SAKK 16/96, SAKK 16/00, SAKK 16/01, and SAKK 16/08 trials': [ESMO Open Volume 7, Issue 2, (2022), 100455].

BACKGROUND: Chemoradiotherapy with durvalumab consolidation has yielded excellent results in stage III non-small-cell lung cancer (NSCLC). Therefore, it is essential to identify patients who might benefit from a surgical approach. MATERIAL AND METHODS: Data from 437 patients with operable stage III NSCLC enrolled in four consecutive Swiss Group for Clinical Cancer Research (SAKK) trials (16/96, 16/00, 16/01, 16/08) were pooled and outcomes were analyzed in 431 eligible patients. All patients were treated with three cycles of induction chemotherapy (cisplatin/docetaxel), followed in some patients by neoadjuvant radiotherapy (44 Gy, 22 fractions) (16/00, 16/01, 16/08) and cetuximab (16/08). RESULTS: With a median follow-up time of 9.3 years (range 8.5-10.3 years), 5- and 10-year overall survival (OS) rates were 37% and 25%, respectively. Overall, 342 patients (79%) underwent tumor resection, with a complete resection (R0) rate of 80%. Patients (n = 272, 63%) with R0 had significantly longer OS compared to patients who had surgery but incomplete resection (64.8 versus 19.2 months, P < 0.001). OS for patients who achieved pathological complete remission (pCR) (n = 66, 15%) was significantly better compared to resected patients without pCR (86.5 versus 37.0 months, P = 0.003). For patients with pCR, the 5- and 10-year event-free survival and OS rates were 45.7% [95% confidence interval (CI) 32.8% to 57.7%] and 28.1% (95% CI 15.2% to 42.6%), and 58.2% (95% CI 45.2% to 69.2%) and 45.0% (95% CI 31.5% to 57.6%), respectively. CONCLUSION: We report favorable long-term outcomes in patients with operable stage III NSCLC treated with neoadjuvant chemotherapy with cisplatin and docetaxel ± neoadjuvant sequential radiotherapy from four prospective SAKK trials. Almost two-third of the patients underwent complete resection after neoadjuvant therapy. We confirm R0 resection and pCR as important predictors of outcome

Long-term outcomes of operable stage III NSCLC in the pre-immunotherapy era: results from a pooled analysis of the SAKK 16/96, SAKK 16/00, SAKK 16/01, and SAKK 16/08 trials.

BACKGROUND Chemoradiotherapy with durvalumab consolidation has yielded excellent results in stage III non-small-cell lung cancer (NSCLC). Therefore, it is essential to identify patients who might benefit from a surgical approach. MATERIAL AND METHODS Data from 437 patients with operable stage III NSCLC enrolled in four consecutive Swiss Group for Clinical Cancer Research (SAKK) trials (16/96, 16/00, 16/01, 16/08) were pooled and outcomes were analyzed in 431 eligible patients. All patients were treated with three cycles of induction chemotherapy (cisplatin/docetaxel), followed in some patients by neoadjuvant radiotherapy (44 Gy, 22 fractions) (16/00, 16/01, 16/08) and cetuximab (16/08). RESULTS With a median follow-up time of 9.3 years (range 8.5-10.3 years), 5- and 10-year overall survival (OS) rates were 37% and 25%, respectively. Overall, 342 patients (79%) underwent tumor resection, with a complete resection (R0) rate of 80%. Patients (n = 272, 63%) with R0 had significantly longer OS compared to patients who had surgery but incomplete resection (64.8 versus 19.2 months, P < 0.001). OS for patients who achieved pathological complete remission (pCR) (n = 66, 15%) was significantly better compared to resected patients without pCR (86.5 versus 37.0 months, P = 0.003). For patients with pCR, the 5- and 10-year event-free survival and OS rates were 45.7% [95% confidence interval (CI) 32.8% to 57.7%] and 28.1% (95% CI 15.2% to 42.6%), and 58.2% (95% CI 45.2% to 69.2%) and 45.0% (95% CI 31.5% to 57.6%), respectively. CONCLUSION We report favorable long-term outcomes in patients with operable stage III NSCLC treated with neoadjuvant chemotherapy with cisplatin and docetaxel ± neoadjuvant sequential radiotherapy from four prospective SAKK trials. Almost two-third of the patients underwent complete resection after neoadjuvant therapy. We confirm R0 resection and pCR as important predictors of outcome