Thoracic malignancies are often a difficult group of tumors to treat definitively as the radiation doses needed to achieve a high probability for tumor control are often associated with high rates of ...radiation-induced toxicities. The lungs are particularly radiosensitive and are susceptible to radiation pneumonitis in the acute and subacute settings and pulmonary fibrosis in the late setting. Acute esophagitis is common and affects patient quality of life. Beyond acute pericarditis, late cardiac toxicities are increasingly being recognized as clinically relevant when delivering thoracic radiotherapy and can affect overall survival. This review details the common and dose-limiting acute and late toxicities associated with thoracic radiation therapy. As radiation-induced toxicities are often amplified with concurrent chemotherapy, this article focuses on the toxicities associated with irradiation for lung cancer, the most common thoracic malignancy, which is often treated with multimodality therapy. The management of radiation-induced toxicities and the changing patterns of toxicities with advanced radiation delivery modalities are also described.
Escalating healthcare costs are necessitating the practice of value-based oncology. It is crucial to critically evaluate the economic impact of influential but expensive therapies such as immune ...checkpoint inhibitors (ICIs). To date, no systematic assessment of the cost-effectiveness (CE) of ICIs has been performed.
PRISMA-guided systematic searches of the PubMed database were conducted. Studies of head/neck (n = 3), lung (n = 5), genitourinary (n = 4), and melanoma (n = 8) malignancies treated with ICIs were evaluated. The reference willingness-to-pay (WTP) threshold was $100,000/QALY.
Nivolumab was not cost-effective over chemotherapy for recurrent/metastatic head/neck cancers (HNCs). For non-small cell lung cancer (NSCLC), nivolumab was not cost-effective for a general cohort, but increased PD-L1 cutoffs resulted in CE. Pembrolizumab was cost-effective for both previously treated and newly-diagnosed metastatic NSCLC. For genitourinary cancers (GUCs, renal cell and bladder cancers), nivolumab and pembrolizumab were not cost-effective options. Regarding metastatic/unresected melanoma, ipilimumab monotherapy is less cost-effective than nivolumab, nivolumab/ipilimumab, and pembrolizumab. The addition of ipilimumab to nivolumab monotherapy was not adequately cost-effective. Pembrolizumab or nivolumab monotherapy offered comparable CE profiles.
With limited data and from the reference WTP, nivolumab was not cost-effective for HNCs. Pembrolizumab was cost-effective for NSCLC; although not the case for nivolumab, applying PD-L1 cutoffs resulted in adequate CE. Most data for nivolumab and pembrolizumab in GUCs did not point towards adequate CE. Contrary to ipilimumab, either nivolumab or pembrolizumab is cost-effective for melanoma. Despite these conclusions, it cannot be overstated that careful patient selection is critical for CE. Future publication of CE investigations and clinical trials (along with longer follow-up of existing data) could substantially alter conclusions from this analysis.
As costs of cancer care rise, the importance of documenting value in oncology increases. Proton beam radiotherapy (PBT) has the potential to reduce toxicities in cancer patients, but is relatively ...expensive and unproven. Evaluating quality of life (QOL) and patient-reported outcomes (PROs) is essential to establishing PBT's "value" in oncologic therapy. The goal of this systematic review was to assess QOL and PROs in patients treated with PBT.
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-guided systematic searches were conducted. The PubMed search engine was the primary data source, along with publications found from references of selected articles, and articles known to the authors published through 2017. Seventeen original investigations were found to have sufficient focus and relevance to be incorporated into the systematic review.
Studies of skull base (n = 1), brain (n = 1), head/neck (n = 1), lung (n = 1), breast (n = 2), prostate (n = 8), and pediatric (n = 3) malignancies treated with PBT that met eligibility criteria were included. QOL did not deteriorate during PBT for skull base and after PBT for brain tumors, respectively. PROs were higher for PBT than photon-based radiotherapy for both head/neck and lung cancer. Patient-reported breast cosmesis was appropriate after PBT and comparable to photon modalities. PBT in various settings of prostate cancer displayed an expected post-therapy decline; one study showed improved PROs (rectal urgency, bowel frequency) for PBT, and two others showed PROs/QOL comparable with other modalities. Pediatric studies demonstrated improvements in QOL during therapy, with additional increases thereafter.
Based on limited data, PBT provides favorable QOL/PRO profiles for select brain, head/neck, lung, and pediatric cancers; measures for prostate and breast cancers were more modest. These results have implications for cost-effective cancer care and prudently designed QOL evaluation in ongoing trials, which are discussed. Future data could substantially change the conclusions of this review.
Liposomes have been extensively studied and are used in the treatment of several diseases. Liposomes improve the therapeutic efficacy by enhancing drug absorption while avoiding or minimizing rapid ...degradation and side effects, prolonging the biological half-life and reducing toxicity. The unique feature of liposomes is that they are biocompatible and biodegradable lipids, and are inert and non-immunogenic. Liposomes can compartmentalize and solubilize both hydrophilic and hydrophobic materials. All these properties of liposomes and their flexibility for surface modification to add targeting moieties make liposomes more attractive candidates for use as drug delivery vehicles. There are many novel liposomal formulations that are in various stages of development, to enhance therapeutic effectiveness of new and established drugs that are in preclinical and clinical trials. Recent developments in multimodality imaging to better diagnose disease and monitor treatments embarked on using liposomes as diagnostic tool. Conjugating liposomes with different labeling probes enables precise localization of these liposomal formulations using various modalities such as PET, SPECT, and MRI. In this review, we will briefly review the clinical applications of liposomal formulation and their potential imaging properties.
To provide evidence-based recommendations to practicing clinicians on management of patients with stage III non-small-cell lung cancer (NSCLC).
An Expert Panel of medical oncology, thoracic surgery, ...radiation oncology, pulmonary oncology, community oncology, research methodology, and advocacy experts was convened to conduct a literature search, which included systematic reviews, meta-analyses, and randomized controlled trials published from 1990 through 2021. Outcomes of interest included survival, disease-free or recurrence-free survival, and quality of life. Expert Panel members used available evidence and informal consensus to develop evidence-based guideline recommendations.
The literature search identified 127 relevant studies to inform the evidence base for this guideline.
Evidence-based recommendations were developed to address evaluation and staging workup of patients with suspected stage III NSCLC, surgical management, neoadjuvant and adjuvant approaches, and management of patients with unresectable stage III NSCLC.Additional information is available at www.asco.org/thoracic-cancer-guidelines.
Highlights • Hyperthermia continues to show clinical benefits in randomized trials across a spectrum of malignancies, with generally well-tolerated side effects when administered as multimodality ...therapy. • Hyperthermia contributes direct tumor cell killing and may also enhance the antitumor effects of chemotherapy and radiation therapy. • Its widespread adoption has been impeded by technological and delivery barriers that are now being addressed through new commercial solutions. • It would serve physicians of all on cological disciplines to stay informed of new developments and consider integrating these promising techniques into their practice.
An adaptive proton therapy workflow using cone beam computed tomography (CBCT) is proposed. It consists of an online evaluation of a fast range-corrected dose distribution based on a virtual CT (vCT) ...scan. This can be followed by more accurate offline dose recalculation on the vCT scan, which can trigger a rescan CT (rCT) for replanning.
The workflow was tested retrospectively for 20 consecutive lung cancer patients. A diffeomorphic Morphon algorithm was used to generate the lung vCT by deforming the average planning CT onto the CBCT scan. An additional correction step was applied to account for anatomic modifications that cannot be modeled by deformation alone. A set of clinical indicators for replanning were generated according to the water equivalent thickness (WET) and dose statistics and compared with those obtained on the rCT scan. The fast dose approximation consisted of warping the initial planned dose onto the vCT scan according to the changes in WET. The potential under- and over-ranges were assessed as a variation in WET at the target's distal surface.
The range-corrected dose from the vCT scan reproduced clinical indicators similar to those of the rCT scan. The workflow performed well under different clinical scenarios, including atelectasis, lung reinflation, and different types of tumor response. Between the vCT and rCT scans, we found a difference in the measured 95% percentile of the over-range distribution of 3.4 ± 2.7 mm. The limitations of the technique consisted of inherent uncertainties in deformable registration and the drawbacks of CBCT imaging. The correction step was adequate when gross errors occurred but could not recover subtle anatomic or density changes in tumors with complex topology.
A proton therapy workflow based on CBCT provided clinical indicators similar to those using rCT for patients with lung cancer with considerable anatomic changes.
Stereotactic body radiation therapy (SBRT) for ≥5 cm lesions is poorly defined, largely owing to the low sample sizes in existing studies. The present analysis examined the SBRT outcomes and assessed ...the effect of chemotherapy in this population.
The National Cancer Data Base was queried for primary non-small cell lung cancer ≥5 cm treated with SBRT (≤10 fractions). Patient, tumor, and treatment parameters were extracted. The primary outcome was overall survival (OS). Statistical methods involved Kaplan-Meier analysis and multivariable Cox proportional hazards modeling.
From 2004 to 2012, data from 201 patients were analyzed. The median follow-up was 41.1 months. The median tumor size was 5.5 cm (interquartile range 5.0-6.0), with cT2a, cT2b, and cT3 disease in 24.9%, 53.2%, and 21.9%, respectively. The median total SBRT dose and fractionation was 50 Gy in 4 fractions, and 92.5% of the patients underwent SBRT with ≤5 fractions. The median OS was 25.1 months. Of the 201 patients, 15% received chemotherapy. The receipt of chemotherapy was associated with longer OS (median 30.6 vs 23.4 months; P=.027). On multivariable analysis, worse OS was seen with increasing age (hazard ratio HR 1.03; P=.012), poorly differentiated tumors (HR 2.06; P=.049), and T3 classification (HR 2.13; P=.005). On multivariable analysis, chemotherapy remained independently associated with improved OS (HR 0.57; P=.039).
SBRT has utility in the setting of tumors ≥5 cm, with chemotherapy associated with improved OS in this subset. These hypothesis-generating data now raise the necessity of performing prospective analyses to determine whether chemotherapy confers outcome benefits after SBRT.
Transmission beams have been proposed for ultra-high dose (or FLASH) proton planning, limiting the organ sparing potentials of proton therapy. By pulling back the ranges of the highest energy proton ...beams and compensating proton ranges to adapt to the target distally, the exit dose of proton beams can be eliminated to better protect organs at risk while still preserving FLASH dose rate delivery.
An inverse planning tool was developed to optimize intensity modulated proton therapy using a single-energy layer for FLASH radiation therapy planning. The range pull-backs were calculated to stop single-energy proton beams at the distal edge of the target. The spot map and weights of each field were optimized to achieve a sufficient dose rate using proton beam Bragg peaks. A C-shape target in phantom, along with 6 consecutive lung cancer patients previously treated using proton stereotactic body radiation therapy were planned using this novel Bragg Peak method and also transmission technique. Dosimetry characteristics and 3-dimensional dose rate were investigated.
The minimum monitor units (MU) for transmission and Bragg peak plans were 400 MU/spot and 1200 MU/spot, respectively, corresponding to spot peak dose rates of 670 GyRBE (relative biological effectiveness) per second and 1950 GyRBE per second. Bragg peak plans yield a generally comparable target uniformity while significantly reducing dose spillage volume from the low to medium dose level. For all the 6 lung cases delivery of 34 GyRBE in 1 fraction, assessing Radiation Therapy Oncology Group 0915 constraints, the lung V
volume was reduced by up to 32% (P = .001) for Bragg peak plans. The transmission plans tended to generate 2.4% higher FLASH dose rate coverage (V
) versus Bragg peak plans over the major organs at risk. However, Bragg peak plans could also reach the FLASH radiation therapy threshold of V
using a higher MU/spot and sophisticated dose-rate optimization algorithm.
This first proof-of-concept study has demonstrated this novel method of combining range pull-back and powerful inverse optimization capable of achieving FLASH dose rate based on currently available machine parameters using a single-energy Bragg peak. Similar target coverage and uniformity can be maintained by Bragg peak FLASH plans while substantially improving the sparing of organs at risk compared with transmission plans.
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