Diagnosis of relevant prostate cancer using supplementary cores from magnetic resonance imaging-prompted areas following multiple failed biopsies

Objectives

To establish the value of MRI in targeting re-biopsy for undiagnosed prostate cancer despite multiple negative biopsies and determine clinical relevance of detected tumors.

Materials and Methods

Thirty-eight patients who underwent MRI after 2 or more negative biopsies due to continued clinical suspicion and later underwent TRUS-guided biopsy supplemented by biopsy of suspicious areas depicted by MRI were identified. Diagnostic performance of endorectal 3T MRI in diagnosing missed cancer foci was assessed using biopsy results as the standard of reference. Ratio of positive biopsies using systematic versus MRI-prompted approaches was compared. Gleason scores of detected cancers were used as surrogate for clinical relevance.

Results

Thirty-four percent of patients who underwent MRI before re-biopsy had prostate cancer on subsequent biopsy. The positive biopsy yield with systematic sampling was 23% versus 92% with MRI-prompted biopsies(p < 0.0001). Seventy-seven percent of tumors were detected exclusively in the MRI-prompted zones. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of MRI to provide a positive biopsy were 92%, 60%, 55%, 94% and 71%, respectively. The anterior gland and apical regions contained most tumors; 75% of cancers detected by MRI-prompted biopsy had Gleason score ≥ 7.

Conclusions

Clinically relevant tumors missed by multiple TRUS-guided biopsies can be detected by a MRI-prompted approach.     

Prostate cancer: comparison of pre-operative 0.35 T MRI with whole-mount histopathology.

Magnetic resonance imaging of the prostate was performed in eight patients prior to radical prostatectomy. The results of the imaging studies were then directly compared to histopathologic findings from whole-mount histologic sections. Magnetic resonance imaging identified 82% of cancers greater than 5 mm in minimal diameter. Cancers were identified as areas of decreased signal intensity compared to the high signal intensity peripheral zone on long TR/TE sequences. Cancers were best detected when they involved the middle level of the gland and the posterior half of the prostate. Of the individual tumors identified by imaging, the amount of tumor involvement was underestimated by 37% and overestimated by 22% by MRI. We conclude that magnetic resonance imaging can identify prostate cancer, but has limitations as a screening modality and in accurately assessing the amount of involvement of the prostate gland by cancer.     

Clinical simulations of prostate radiotherapy using BOMAB-like phantoms: Results for neutrons

This paper presents in-phantom photoneutron equivalent doses induced by external radiotherapy, these are necessary to assess organ-averaged equivalent doses to derive the risk of secondary cancer development, associated with non-target organ exposures. The measurements were performed by Working Group 9 “Radiation Protection Dosimetry in Medicine” of the European Radiation Dosimetry Group (EURADOS) for simulations of clinical radiotherapy treatments of prostate cancer. The photoneutron dose measurements were carried out in a BOMAB-like water-filled phantom, by means of superheated emulsions (superheated drop detectors SDD and bubble damage BTI^® detectors) and Poly-Allyl-Diglicol-Carbonate (PADC) solid state nuclear track detectors. Dose data were acquired in a three-dimensional matrix of reproducible measurement points, which are spaced according to detectors size. Four clinical protocols for the treatment of the prostate tumor were considered and compared, by measuring the doses delivered to the planning target volume (PTV) and to peripheral radiosensitive regions (i.e. colon-rectum and bladder). The clinical irradiations were performed in two clinical radiotherapy facilities based on Varian Clinac 2300 CD accelerator: Santa Chiara University Hospital (Pisa, Italy) and Centre of Oncology M. Skłodowska-Curie Memorial Institute (Krakow, Poland). An additional tomotherapy prostate cancer treatment was also simulated in Campo di Marte Hospital (Lucca, Italy). Radiation qualities of 6, 12, 15, 18 and 20 MV were used; all of these are capable of producing photoneutrons. Data from this work span most of the X-ray beam energies and prostate treatment modalities used in the current clinical practice. These data permit the assessment of doses absorbed by a radiotherapy patient either at the treatment volume or at out-of-field organs. Comparison of different dosimeters, under the same irradiation conditions, showed that dosimeters generally agreed within their 20% 1 SD uncertainty. Comparison of different treatment modalities in the two contributing clinical centers (Pisa and Krakow) were also possible, as well as a comparison of dose profiles resulting from the different treatment techniques, delivered at the same primary photon energy. It was in particular found that photon acceleration energies as low as 6 MV are able to produce a non-negligible photoneutron component, which causes an undue dose to the patient of the order of tens microsievert per unit photon dose delivered at the target volume.     

In vivo differential diagnosis of prostate cancer and benign prostatic hyperplasia: localized proton magnetic resonance spectroscopy using external-body surface coil

Localized proton-stimulated echo acquisition mode (STEAM) spectroscopy was performed in seven patients with benign prostatic hyperplasia (BPH), six patients with prostate cancer, and seven healthy volunteers to determine whether citrate levels detected using a saddle-type external-body surface coil (two loops of 13 cm ×17 cm) could reliably discriminate BPH from prostatic cancer. Relative area ratios of citrate level to choline plus creatine or citrate to lipid signal were compared with postoperative pathologic histology findings. The metabolic signals were well detectable as much as the line width of water resonance was ranging from 5 to 9 hz. Average SNRs of citrate in BPH and prostate cancer were 11.4 and 1.9, respectively. The major finding was consistently lower citrate levels in prostate cancer compared with BPH and normal prostate central gland. This was significantly (p < 0.01) reflected by lower mean citrate/[creatine+choline] peak area ratio and citrate/lipid peak area ratio observed for region of cancer (0.446 ± 0.063, 0.097 ± 0.030) compared with BPH (1.458 ± 0.107, 0.786 ± 0.162) and normal central gland (1.418 ± 0.129, 0.175 ± 0.011), respectively. These studies demonstrate the potential of citrate spectrum detected by an external-body surface coil as an in vivo marker for discriminating prostate cancer from BPH.     

Heavy-ion cancer therapy

The HIMAC Heavy-Ion Medical Accelerator in Chiba was completed in 1993, and clinical trials of particle radiotherapy for cancer were started using carbon beams accelerated by HIMAC in 1994. Since then, about 2200 patients have been treated in the carbon radiotherapy up to the end of February 2005. A heavy-ion beam generates a Bragg peak in a medium, and it provides biological effects of high RBE and low OER in the Bragg peak region. In heavy-ion radiotherapy, therefore, the beam delivers a high radiation dose to a target volume highly locally. These are excellent advantages for radiotherapy over the case of X-rays. The clinical trials have proved that carbon radiotherapy brings various good results.     

Study of ProtoPorphyrin IX Elimination by Body Excreta: A new Noninvasive Cancer Diagnostic Method?

This paper describes the elimination of porphyrins by feces. It was demonstrated that porphyrin accumulates substantially more in tumors than in normal tissues, and consequently more PPIX reaches the blood of patients and animals with tumors, and then, it needs to be eliminated. The fluorescence of feces revealed that there are large amounts of PPIX in the excreta of animals with cancer comparing with healthy animals. The autofluorescence of feces porphyrin extracted with acetone was analyzed using fluorescence spectroscopy of animals inoculated with DU145 cells into the prostate and healthy animals to monitor the PPIX concentration. Emission spectra were obtained by exciting the samples at 405 nm. Significant differences were observed in autofluorescence intensities measured in the 575–725 nm spectral regions for the studied groups. The results showed a noninvasive, simple, rapid and sensitive method to detect cancer by feces analysis.     

Assessment of cancer risk from neutron exposure – The ANDANTE project

The ANDANTE project began in January 2012 as a spin-off of results of an earlier Euratom project, ALLEGRO, designed to address the problems of medium- and long-term risks following radiotherapy. ANDANTE will investigate the relative risk of induction of cancer from exposure to neutrons compared to photons. The project will focus on three specific cancers that may be detected as second malignant neoplasms following paediatric radiotherapy: salivary gland, thyroid gland, and breast tissue. Stem cells from each of the types of tissue will be exposed to well characterised beams of both neutrons and photons. Biological markers of possible tumorigenesis will be used to develop RBE models for neutrons. The experimental beams will be measured in terms of fluence and energy spectra in order to provide date for a track structure model, which will be developed to simulate the exact experimental conditions and to explore the relationships between exposure parameters and response. The RBE model will be utilized in the assessment of follow-up data from paediatric photon radiotherapy patients. The out-of-beam mixed photon-neutron fields generated during proton therapy will be measured in phantoms, and an analytic algorithm will be developed for reconstructing the fields distant from the treatment site using data available from clinical records. One of the aims of the project is a critical analysis of the potential power of a multi-centre cohort of paediatric patients to give confidence in the neutron risk estimates in radiotherapy patients.This paper focuses on the challenges in the ANDANTE project posed by the need to know detailed neutron, photon, and charged particle fluences and energy spectra in order to determine the neutron RBE as a function of dose and energy.     

Apparent diffusion coefficient of line scan diffusion image in normal prostate and prostate cancer—comparison with single-shot echo planner image

Purpose

This retrospective study was designed to evaluate the apparent diffusion coefficient (ADC) of line scan diffusion images (LSDI) in normal prostate and prostate cancer. Single-shot echo planner images (SS-EPI) were used for comparison.

Materials and Methods

Twenty prostate tumors were examined by conventional MRI in 14 patients prior to radical prostatectomy. All patients were examined with a 1.5-T MR imager (Signa CV/i ver. 9.1 GE Medical System Milwaukee, WI, USA). Diffusion-weighted MR imaging (DWI) using LSDI was performed with a pelvic phased-array coil, with b values of 5 and 800 s/mm². DWI using SS-EPI was performed with a body coil, with b values of 0 and 800 s/mm². The ADCs of each sequence for 14 normal prostate and 20 prostate cancers were histopathologically assessed. Signal-to-noise ratio (SNR) on DWI was estimated and compared for each sequence.

Results

The mean ADCs (±S.D.) of normal peripheral zones (PZ), transition zones (TZ) and cancer (in 10⁻³ mm²/s) that used LSDI were 1.42±0.12, 1.23±0.10 and 0.79±0.19, respectively. Those that used SS-EPI were 1.76±0.26, 1.38±0.20 and 1.05±0.27, respectively. Using unpaired t test (P<.05), we found a significant difference in each sequence between normal tissue (both PZ and TZ) and the cancer. Paired t test (P<.05) also registered a significant difference between LSDI and SS-EPI. Mean SNR for DWI using LSDI was 16.49±5.03, while the DWI using SS-EPI was 18.85±9.26. The difference between the SNR of each sequence was not statistically significant by paired t test.

Conclusion

We found that ADCs using LSDI and SS-EPI showed similar tendencies in the same patients. However, in all regions, LSDI ADCs had smaller standard deviations than SS-EPI ADCs.     

Photo-activated pheophorbide a inhibits the growth of prostate cancer cells

Pheophorbide a (PhA) was identified as a photosensitizer to exert cytotoxicity on tumor cells. However, the efficacy of this compound on the treatment of prostate cancer remains unknown. The aim of this study was to evaluate the photodynamic effect of PhA on prostate cancer cells. Cellular uptake of PhA and cell viability after photo-activation was studied in LNCaP prostate cancer cells. The corresponding production of reactive oxygen species within cells was determined after photodynamic therapy (PDT). Our results showed that the uptake of PhA into LNCaP cells was in a time-dependent manner and the cytotoxicity of PhA-PDT was photosensitizer dose- and light dose-dependent. The intracellular reactive oxygen species was remarkably induced after PDT treatment, which was responsible for the inhibition effect on prostate cancer cells. This is the first report to evaluate the photodynamic effect of PhA on prostate cancer. Our findings demonstrate that PhA-PDT may be a potentially promising treatment for localized prostate cancer, which can be a therapeutic option after the failures of radiotherapy and hormone therapy.     

Two-dimensional spectroscopic imaging for pretreatment evaluation of prostate cancer: comparison with the step-section histology after radical prostatectomy

Purpose

To minimize user and vendor dependence of the spectrum processing of prostate spectra, to measure the ratio of choline (Cho) plus creatine (Cr) to citrate (Cit) in the prostate tissue of normal volunteers and cancer patients, and to compare the results with pathologic findings after radical prostatectomy.

Materials and methods

Four healthy volunteers and 13 patients with prostate cancer were measured. Measurements were performed using two-dimensional magnetic resonance spectroscopic imaging (MRSI) and endorectal coil. A standard vendor's spectrum processing approach has been modified. An original feature of this methodology was the combination of vendor-optimized and user-independent spectrum preprocessing in the scanner and user-independent quantitation in the environment of an MRUI software package. (Cho+Cr)/Cit ratio was used for the classification of prostate tissue. Results were compared with histopathology after radical prostatectomy.

Results

Eight of 13 cancer patients were classified as suspicious or very suspicious for cancer at spectroscopy, three were ambiguous for cancer and two patients were evaluated as false negative. A considerable overlap of metabolite ratios at various Gleason score was found.

Conclusion

The proposed spectrum processing has the potential to improve the accuracy and user independency of the (Cho+Cr)/Cit quantitation. This study confirmed the previous results that a considerable overlap of (Cho+Cr)/Cit ratios exists at various Gleason score levels.     

Coupled Feedback Loops Involving PAGE4, EMT and Notch Signaling Can Give Rise to Non-Genetic Heterogeneity in Prostate Cancer Cells

Non-genetic heterogeneity is emerging as a crucial factor underlying therapy resistance in multiple cancers. However, the design principles of regulatory networks underlying non-genetic heterogeneity in cancer remain poorly understood. Here, we investigate the coupled dynamics of feedback loops involving (a) oscillations in androgen receptor (AR) signaling mediated through an intrinsically disordered protein PAGE4, (b) multistability in epithelial–mesenchymal transition (EMT), and (c) Notch–Delta–Jagged signaling mediated cell-cell communication, each of which can generate non-genetic heterogeneity through multistability and/or oscillations. Our results show how different coupling strengths between AR and EMT signaling can lead to monostability, bistability, or oscillations in the levels of AR, as well as propagation of oscillations to EMT dynamics. These results reveal the emergent dynamics of coupled oscillatory and multi-stable systems and unravel mechanisms by which non-genetic heterogeneity in AR levels can be generated, which can act as a barrier to most existing therapies for prostate cancer patients.     

What can we learn from the neutron clinical experience for improving ion-beam techniques and high-LET patient selection?

Historically, improvements in radiotherapy have been mainly due to improvements in physical selectivity: beam penetration, collimation, dosimetry, treatment planning; and advances in imaging. Neutrons were the first high-LET (linear energy transfer) radiation to be used clinically and showed improvement in the differential response of radiation resistant tumors and normal tissues. The benefits of fast neutrons (and other forms of high LET radiations) are due to their biological effects: a reduction of the OER, a reduction in the differential cell radiosensitivity related to their position in the mitotic cycle, and a reduction in cellular repair capacity (thus less importance of fractionation). The poor physical selectivity of the early neutron therapy beams introduced a systematic bias in comparison with the photon treatments and created a negative perception for neutron therapy. However, significant improvements in the neutron therapy equipment resulted in a physical selectivity similar to modern MV photon therapy.The tumor types or sites where the best therapeutic results were obtained included inoperable or recurrent salivary gland tumors locally extended prostatic adenocarcinomas, and slowly growing well-differentiated sarcomas. The benefit of neutrons for some other well-defined groups of patients was demonstrated in randomized trials. It was estimated that about 20 % of all radiotherapy patients could benefit from fast neutrons (if neutrons are delivered under satisfactory physical conditions). An important issue for fast neutron therapy is the selection of the types of patients who could most benefit from high-LET radiations. The same issue is raised today with other high-LET radiations (e.g., ¹²C ions). It is reasonable to assume that the same types of patients would benefit from ¹²C irradiation. Of course the better physical selectivity of ion beams enhances the treatment possibilities but this is true for both the high-LET and low-LET radiations (i.e., moving from neutrons to ¹²C ions and from photons to protons, respectively). An important area of research involves developing criteria to identify specific patients suitable for high-LET radiation. One promising technique is to measure the RBE of the cancer cell population in vitro mainly in head and neck tumors. Modern molecular imaging allows the identification of hypoxic or proliferative regions in the tumor. Special MRI examinations are also able to identify hypoxic regions. A promising predictive test recently initiated, is the study of non-repairable double strand breaks but the utility of the technique needs to be confirmed. The extensive experience with fast neutron therapy can greatly assist the transition to high-LET charged-particle therapy.     

Implementation of nanoparticles in therapeutic radiation oncology

Development and progress of cancer is a very complex disease process to comprehend because of the multiple changes in cellular physiology, pathology, and pathophysiology resulting from the numerous genetic changes from which cancer originates. As a result, most common treatments are not directed at the molecular level but rather at the tissue level. While personalized care is becoming an increasingly aim, the most common cancer treatments are restricted to chemotherapy, radiation, and surgery, each of which has a high likelihood of resulting in rather severe adverse side effects. For example, currently used radiation therapy does not discriminate between normal and cancerous cells and greatly relies on the external targeting of the radiation beams to specific cells and organs. Because of this, there is an immediate need for the development of new and innovative technologies that help to differentiate tumor cells and micrometastases from normal cells and facilitate the complete destruction of those cells. Recent advancements in nanoscience and nanotechnology have paved a way for the development of nanoparticles (NPs) as multifunctional carriers to deliver therapeutic radioisotopes for tumor targeted radiation therapy, to monitor their delivery, and improve the therapeutic index of radiation and tumor response to the treatment. The application of NPs in radiation therapy has aimed to improve outcomes in radiation therapy by increasing therapeutic effect in tumors and reducing toxicity on normal tissues. Because NPs possess unique properties, such as preferential accumulation in tumors and minimal uptake in normal tissues, it makes them ideal for the delivery of radiotherapy. This review provides an overview of the recent development of NPs for carrying and delivering therapeutic radioisotopes for systemic radiation treatment for a variety of cancers in radiation oncology.     

Anticancer Activity of Copper Complex of (4R)-(-)-2-Thioxo-4-thiazolidinecarboxylic Acid and 3-Rhodaninepropionic Acid on Prostate and Breast Cancer Cells by Fluorescent Microscopic Imaging

Copper complexes with strong anticancer activity are promising new drugs for treatment of patients with metastatic cancer. Copper 8-hydroxyquinoline-2-carboxaldehyde-thiosemicarbazide (CuHQTS) and copper 8-hydroxyquinoline-2-carboxaldehyde-4,4-dimethyl-3-thiosemicarbazide (CuHQDMTS) were found to have strong anticancer activity against cisplatin-resistant neuroblastoma cells and prostate cancer cells. This study aimed to synthesize and characterize two new anticancer copper complexes, copper complex of (4R)-(?)-2-Thioxo-4-thiazolidinecarboxylic acid (CuTTDC), and copper complex of 3-Rhodaninepropionic acid-copper complex (CuRDPA). Cell growth inhibition and cytotoxicity of CuTTDC and CuRDPA on prostate and breast cancer cells were evaluated with Cell Counting Kits-8 (CCK8) assay and fluorescent microscopic imaging respectively. Strong anticancer activity of CuTTDC and CuRDPA was demonstrated by growth inhibition and cytotoxicity of prostate and breast cancer cells treated with these two copper complexes, supporting further investigation of potential use of these two new anticancer complexes for treatment of prostate and breast cancer metastasis.     

Cancer cell recognition--mechanical phenotype

The major characteristics of cancer metastasis is the ability of the primary tumor cells to migrate by way of the blood or lymph vessels and to form tumors at multiple, distant sites. There are evidences that cancer progression is characterized by disruption and/or reorganization of cytoskeleton (i.e. cellular scaffold). This is accompanied by various molecular alterations influencing the overall mechanical resistance of cells. Current approach in diagnosis focuses mainly on microbiological, immunological, and pathological aspects rather than on the biomechanics of diseases. The determination of mechanical properties of an individual living cell has became possible with the development of local measurement techniques, such as atomic force microscopy, magnetic or optical tweezers. The advantage of them lies in the capability to measure living cells at a single cell level and in liquid conditions, close to natural environment. Here, we present the studies on mechanical properties of single cells originating from various cancers. The results show that, independently of the cancer type (bladder, melanoma, prostate, breast and colon), single cells are characterized by the lower Young's modulus, denoting higher deformability of cancerous cells. However, the obtained Young's modulus values were dependent on various factors, like the properties of substrates used for cell growth, force loading rate, or indentation depth. Their influence on elastic properties of cells was considered. Based on these findings, the identification of cancerous cells based on their elastic properties was performed. These results proved the AFM capability in recognition of a single, mechanically altered cell, also in cases when morphological changes are not visible. The quantitative analysis of cell deformability carried out using normal (reference) and cancerous cells and, more precisely, their characterization (qualitative and quantitative) can have a significant impact on the development of methodological approaches toward precise identification of pathological cells and would allow for more effective detection of cancer-related changes.     

Field-map correction in read-out segmented echo planar imaging for reduced spatial distortion in prostate DWI for MRI-guided radiotherapy applications

Diffusion-weighted echo planar imaging (DW-EPI) suffers from geometric distortion due to low phase-encoding bandwidth. Read-out segmented echo planar imaging (RS-EPI) reduces distortion but residual distortion remains in extreme cases. Additional corrections need to be applied, especially for radiotherapy applications where a high degree of accuracy is needed. In this study the use of magnetic field map corrections are assessed in DW-EPI and RS-EPI, to reduce geometric uncertainty for MRI-guided radiotherapy applications. Magnetic field maps were calculated from gradient echo images and distortion corrections were applied to RS-EPI images. Distortions were assessed in a prostate phantom by comparing to the known geometry, and in vivo using a modified Hausdorff distance metric using a T2-weighted spin echo as ground truth. Across 10 patients, field map-corrected RS-EPI reduced maximum distortion by 5 mm on average compared to DW-EPI (σ = 1.9 mm). Geometric distortions were also reduced significantly using field mapping with RS-EPI, compared to RS-EPI alone (p ≤ 0.05). The increased geometric accuracy of these techniques can potentially allow diffusion-weighted images to be fused with other MR or CT images for radiotherapy treatment purposes.     

Fission neutron therapy at FRM II: Indications and first results

Based on 15 years of experience with neutron therapy at the former facility at Munich research reactor FRM, fast neutron therapy with fission neutrons of FRM II is performed at the new facility MedApp since June 2007. General indications are superficially located tumors with insufficient response to conventional radiotherapy. Until August 2009, 58 patients were treated, 25% of them with curative intention (adenoid cystic carcinoma of major salivary glands, malignant melanoma, sarcoma). The most frequent palliative indications were breast wall recurrences of breast cancer and skin or lymph node recurrences of squamous cell carcinomas, resulting in response rates of 84% and 42%, respectively. Short treatment times of fast neutron therapy (3–5 fractions in 2–3 weeks) are advantageous in palliative treatment strategies.     

Engineering Multifunctional Gold Decorated Dendritic Mesoporous Silica/Tantalum Oxide Nanoparticles for Intraperitoneal Tumor‐Specific Delivery

Nonspecific high‐energy radiation for treatment of metastatic ovarian cancer is limited by damage to healthy organs, which can be mitigated by the use of radiosensitizers and image‐guided radiotherapy. Gold (Au) and tantalum oxide (TaO_x) nanoparticles (NPs), by virtue of their high atomic numbers, find utility in the design of bimetallic NP systems capable of high‐contrast computed tomography (CT) imaging as well as a potential radiosensitizing effect. These two radio‐dense metals are integrated into dendritic mesoporous silica NPs (dMSNs) with radial porous channels for high surface‐area loading of therapeutic agents. This approach results in stable, monodispersed dMSNs with a uniform distribution of Au on the surface and TaO_x in the core that exhibits CT attenuation up to seven times greater than iodine or monometallic dMSNs without either TaO_x or Au. Tumor targeting is assessed in a metastatic ovarian cancer mouse model. Ex vivo micro‐CT imaging of collected tumors shows that these NPs not only accumulate at tumor sites but also penetrate inside tumor tissues. This study demonstrates that after intraperitoneal administration, rationally designed bimetallic NPs can simultaneously serve as targeted contrast agents for imaging tumors and to enhance radiation therapy in metastatic ovarian cancer.     

Combinational Chemotherapy and Photothermal Therapy Using a Gold Nanorod Platform for Cancer Treatment

Multimodal approaches combined with various nanomaterials and advanced techniques have been developed for synergistic cancer treatment. Among various therapies, conventional chemotherapy (CHT) is a direct cancer treatment that can produce unintended side effects due to nonspecific action on both the tumor and normal cells; patient-friendly photothermal therapy (PTT) may be able to treat embedded tumors in vital regions with minimal invasion but does not guarantee complete removal of cancers. However, the combination of CHT-PTT may provide a promising tool for direct cancer treatment with minimal side effects. In this regard, nanostructured materials, such as gold nanorods with tuned size and surface characteristics, are key components designed to enhance the heating capacity and active or passive delivery of drugs to the tumor site. In this review, the pioneering work synergizing CHT and PTT is summarized, and the current state-of-the-art in the development of inorganic and organic nanocomposites for combinational therapy is described.