A Dose Falloff Gradient Study in RapidArc Planning of Lung Stereotactic Body Radiation Therapy

Introduction: Radiation Therapy Oncology Group (RTOG) report #0813 and 0915 recommends using D2cm and R50% as plan quality metrics for evaluation of normal tissue sparing in stereotactic body radiation therapy (SBRT) of lung lesion. This study introduces dose falloff gradient (DFG) as a tool for analyzing the dose beyond the planning target volume (PTV) extending into normal tissue structures. In ascertaining the impact of PTV size and SBRT planning techniques in DFG, this study questions the independence of the RTOG recommended metrics. Materials and Methods: In this retrospective study, 41 RapidArc lung SBRT plans with 2 or 3 complete or partial arcs were analyzed. PTV volumes ranged between 5.3 and 113 cm3 and their geographic locations were distributed in both lungs. 6MV, 6 MV-FFF, 10 MV, or 10 MV-FFF energies were used. RTOG-0915 metrics conformity index, homogeneity index, D2cm, R50%, and HDloc were evaluated. DFG was computed from the mean and maximum dose in seven concentric 5 mm wide rings outside the PTV. DFG was investigated against the volume of normal lung irradiated by 50% isodose volume. Treatment plans with alternate energy and couch rotations were generated. Results: The dose falloff beyond PTV was modeled using a double exponential fit and evaluated for relationship with intermediate lung dose. Photon energy and beam configuration had a minimal impact on the dose falloff outside. The product of normalized D2cm and R50% was estimated to have a slowly varying value. Conclusions: Dose falloff outside PTV has been studied as a function of radial distance and ascertained by intermediate dose to normal lung. DFG can serve as a complementary plan quality metric

A comparative study to evaluate the efficacy of on board imaging with cone beam CT using target registration in patients with lung tumors undergoing stereotactic body radiation therapy and comparison with ExacTrac using skeletal registration on Novalis Tx

Background: Stereotactic body radiation therapy is an advanced technique, which delivers ablative doses to lung lesions. Target verification is done either by orthogonal x-rays or cone beam CT. This study was undertaken to compare these two verification methods. Aim: To evaluate the efficacy of ExacTrac and Cone Beam Computed Tomography (CBCT) for target repositioning while delivering Stereotactic Body Radiation Therapy (SBRT) for lung lesions and derive the population-based margin. Materials and Methods: All patients who had undergone SBRT for lung lesions from February to September 2009 were involved. Patients were immobilized using the BodyFix double vacuum immobilization system, indexed to the computed tomography (CT) simulator and treatment machine. Four-dimensional (3-D) scan was done to generate internal target volume (ITV) and a free breathing CT scan for planning was done on the BrainLab iPlan 4.1 software. During treatment, patient′s position was verified using ExacTrac and CBCT. The resulting vertical, lateral, and longitudinal shifts were noted. The random and systematic error were calculated and the margin recipe derived using the Van Herk formula. Results: Sixteen patients had undergone SBRT for lung tumors from February to September 2009. Data from eight patients who had undergone 34 sessions of SBRT was analyzed. The systematic error for lateral, longitudinal, and vertical shifts for ExacTrac and CBCT were 3.68, 4.27, 3.5 mm and 0.53, 0.38, 0.70 mm, respectively. The random error were 1.10, 1.51, 1.96 mm and 0.32, 0.81, 0.59 mm. The lateral, longitudinal and vertical Van Herk margin recipe for ExacTrac were 9.98, 11.72, 10.18 mm, respectively, and for CBCT was 2.17, 1.53,1.55 mm. Conclusions: The systematic and random errors for CBCT were significantly lesser as compared to the errors with Exactrac

A dose falloff gradient study in RapidArc planning of lung stereotactic body radiation therapy

Introduction: Radiation Therapy Oncology Group (RTOG) report #0813 and 0915 recommends using D2cmand R50%as plan quality metrics for evaluation of normal tissue sparing in stereotactic body radiation therapy (SBRT) of lung lesion. This study introduces dose falloff gradient (DFG) as a tool for analyzing the dose beyond the planning target volume (PTV) extending into normal tissue structures. In ascertaining the impact of PTV size and SBRT planning techniques in DFG, this study questions the independence of the RTOG recommended metrics. Materials and Methods: In this retrospective study, 41 RapidArc lung SBRT plans with 2 or 3 complete or partial arcs were analyzed. PTV volumes ranged between 5.3 and 113 cm3 and their geographic locations were distributed in both lungs. 6MV, 6 MV-FFF, 10 MV, or 10 MV-FFF energies were used. RTOG-0915 metrics conformity index, homogeneity index, D2cm, R50%, and HDlocwere evaluated. DFG was computed from the mean and maximum dose in seven concentric 5 mm wide rings outside the PTV. DFG was investigated against the volume of normal lung irradiated by 50% isodose volume. Treatment plans with alternate energy and couch rotations were generated. Results: The dose falloff beyond PTV was modeled using a double exponential fit and evaluated for relationship with intermediate lung dose. Photon energy and beam configuration had a minimal impact on the dose falloff outside. The product of normalized D2cmand R50%was estimated to have a slowly varying value. Conclusions: Dose falloff outside PTV has been studied as a function of radial distance and ascertained by intermediate dose to normal lung. DFG can serve as a complementary plan quality metric

Stem Cell Origin of Cancer: Implications of Oncogenesis Recapitulating Embryogenesis in Cancer Care

From this perspective, we wonder about the clinical implications of oncology recapturing ontogeny in the contexts of neoantigens, tumor biomarkers, and cancer targets. We ponder about the biological ramifications of finding remnants of mini-organs and residuals of tiny embryos in some tumors. We reminisce about classical experiments showing that the embryonic microenvironment possesses antitumorigenic properties. Ironically, a stem-ness niche—in the wrong place at the wrong time—is also an onco-niche. We marvel at the paradox of TGF-beta both as a tumor suppressor and a tumor promoter. We query about the dualism of EMT as a stem-ness trait engaged in both normal development and abnormal disease states, including various cancers. It is uncanny that during fetal development, proto-oncogenes wax, while tumor-suppressor genes wane. Similarly, during cancer development, proto-oncogenes awaken, while tumor-suppressor genes slumber. Importantly, targeting stem-like pathways has therapeutic implications because stem-ness may be the true driver, if not engine, of the malignant process. Furthermore, anti-stem-like activity elicits anti-cancer effects for a variety of cancers because stem-ness features may be a universal property of cancer. When a fetus survives and thrives despite immune surveillance and all the restraints of nature and the constraints of its niche, it is a perfect baby. Similarly, when a neoplasm survives and thrives in an otherwise healthy and immune-competent host, is it a perfect tumor? Therefore, a pertinent narrative of cancer depends on a proper perspective of cancer. If malignant cells are derived from stem cells, and both cells are intrinsically RB1 negative and TP53 null, do the absence of RB1 and loss of TP53 really matter in this whole narrative and an entirely different perspective of cancer

Stem Cell Origin of Cancer: Clinical Implications for Cancer Immunity and Immunotherapy

A simple way to understand the immune system is to separate the self from non-self. If it is self, the immune system tolerates and spares. If it is non-self, the immune system attacks and destroys. Consequently, if cancer has a stem cell origin and is a stem cell disease, we have a serious problem and a major dilemma with immunotherapy. Because many refractory cancers are more self than non-self, immunotherapy may become an uphill battle and pyrrhic victory in cancer care. In this article, we elucidate cancer immunity. We demonstrate for whom, with what, as well as when and how to apply immunotherapy in cancer care. We illustrate that a stem cell theory of cancer affects our perspectives and narratives of cancer. Without a pertinent theory about cancer’s origin and nature, we may unwittingly perform misdirected cancer research and prescribe misguided cancer treatments. In the ongoing saga of immunotherapy, we are at a critical juncture. Because of the allure and promises of immunotherapy, we will be treating more patients not immediately threatened by their cancer. They may have more to lose than to gain, if we have a misconception and if we are on a wrong mission with immunotherapy. According to the stem cell theory of cancer, we should be careful with immunotherapy. When we do not know or realize that cancer originates from a stem cell and has stem-ness capabilities, we may cause more harm than good in some patients and fail to separate the truth from the myth about immunotherapy in cancer care

Robust optimization in lung treatment plans accounting for geometric uncertainty.

Robust optimization generates scenario-based plans by a minimax optimization method to find optimal scenario for the trade-off between target coverage robustness and organ-at-risk (OAR) sparing. In this study, 20 lung cancer patients with tumors located at various anatomical regions within the lungs were selected and robust optimization photon treatment plans including intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) plans were generated. The plan robustness was analyzed using perturbed doses with setup error boundary of ±3 mm in anterior/posterior (AP), ±3 mm in left/right (LR), and ±5 mm in inferior/superior (IS) directions from isocenter. Perturbed doses for D99 , D98 , and D95 were computed from six shifted isocenter plans to evaluate plan robustness. Dosimetric study was performed to compare the internal target volume-based robust optimization plans (ITV-IMRT and ITV-VMAT) and conventional PTV margin-based plans (PTV-IMRT and PTV-VMAT). The dosimetric comparison parameters were: ITV target mean dose (Dmean ), R95 (D95 /Dprescription ), Paddick's conformity index (CI), homogeneity index (HI), monitor unit (MU), and OAR doses including lung (Dmean , V20 Gy and V15 Gy ), chest wall, heart, esophagus, and maximum cord doses. A comparison of optimization results showed the robust optimization plan had better ITV dose coverage, better CI, worse HI, and lower OAR doses than conventional PTV margin-based plans. Plan robustness evaluation showed that the perturbed doses of D99 , D98 , and D95 were all satisfied at least 99% of the ITV to received 95% of prescription doses. It was also observed that PTV margin-based plans had higher MU than robust optimization plans. The results also showed robust optimization can generate plans that offer increased OAR sparing, especially for normal lungs and OARs near or abutting the target. Weak correlation was found between normal lung dose and target size, and no other correlation was observed in this study