Does prophylactic negative pressure wound therapy prevent surgical site infection in abdominal surgery?

OBJECTIVE: To determine if prophylactic negative pressure wound therapy (pNPWT) allows for the prevention of surgical site infections (SSIs) in abdominal surgery. METHOD: A non-systematic review assessing the evidence was conducted in 2020. RESULTS: Retrospectve studies comparing patients with pNPWT with patients receiving standard wound dressing after abdominal surgery showed encouragning results in favour of pNPWT for reducing the incidence of SSIs, but randomised controlled trials have so far reported mixed results. CONCLUSION: New randomised controlled trials including a sufficient number of patients at risk of SSIs are needed for confirming the results of non-interventional studies.

Highlighting the Place of Metastasis-Directed Therapy in Isolated Liver Metastases in Prostate Cancer: A Case Report.

Metastatic prostate cancer remains a challenge for clinicians. Metastases involve mainly the bone compartment and can manifest as oligometastatic disease. In this setting, the role of metastasis-directed therapies (MDT) including surgery and/or stereotactic body radiotherapy is currently evaluated. Visceral metastases are less common and have very poor prognosis in mPC. Whether treating isolated visceral metastases such as liver metastases with MDT could increase the prognosis remains unknown. We report the management of a prostate cancer patient who progressed on androgen deprivation therapy with apparition of two liver metastases. We describe the feasibility of combining MDT with abiraterone acetate and prednisone in a patient with metastatic castration-resistant prostate cancer. MDT allowed the interruption of abiraterone acetate, preventing cumulative toxicity of this agent.

Do refined consensus guidelines improve the uniformity of clinical target volume delineation for rectal cancer? Results of a national review project.

In a previous national central review project, 74% of the rectal cancer clinical target volumes (CTVs) needed a modification. In a follow-up initiative, we evaluated whether the use of refined international consensus guidelines improves the uniformity of CTV delineation in clinical practice.

Evaluation of a dedicated brain metastases treatment planning optimization for radiosurgery: a new treatment paradigm?

PURPOSE: To investigate the feasibility of a novel dedicated treatment planning solution, to automatically target multiple brain metastases with a single isocenter and multiple inversely-optimized dynamic conformal arcs (DCA), and to benchmark it against the well-established multiple isocenter DCA (MIDCA) and volumetric modulated arc therapy (VMAT) approaches. MATERIAL AND METHODS: Ten previously treated patients were randomly selected, each representing a variable number of lesions ranging between 1 to 8. The original MIDCA treatments were replanned with both VMAT and the novel brain metastases tool. The plans were compared by means of Paddick conformity (CI) and gradient index (GI), and the volumes receiving 10 Gy (V10) and 12 Gy (V12). RESULTS: The brain metastases software tool generated plans with similar CI (0.65 ± 0.08) as both established treatment techniques while improving the gradient (mean GI = 3.9 ± 1.4). The normal tissue exposure in terms of V10 (48.5 ± 35.9 cc) and V12 (36.3 ± 27.1 cc) compared similarly to the MIDCA technique and surpassed VMAT plans. CONCLUSIONS: The automated brain metastases planning algorithm software is an optimization of DCA radiosurgery by increasing delivery efficiency to the level of VMAT approaches. Improving dose gradients and normal tissue sparing over VMAT, revives DCA as the paradigm for linac-based stereotactic radiosurgery of multiple brain metastases.

Unusual presentation of bladder cancer resurgence and efficacy of radiotherapy.

A 68-year-old man with a history of bladder cancer presented with perineal pain and penile priapism. The work up showed multiple lesions strictly located in the penis; biopsy confirmed metastases of bladder cancer. Surgery was judged unfeasible and chemotherapy failed to improve symptoms. Radiotherapy was therefore delivered on the whole penis and resulted in a rapid clinical benefit and persistent control of the disease. Penile metastases are very rare and no consensus exists concerning their management; radiotherapy appears as a promising therapeutic option not only to palliate pain but also to control the disease.

Phase II study of helical tomotherapy in the multidisciplinary treatment of oligometastatic colorectal cancer.

BACKGROUND: Complete metastasectomy provides a real chance for long-term survival in patients with oligometastatic colorectal cancer (CRC). For inoperable patients, we evaluated in this study intensity-modulated and image-guided radiotherapy (IMRT-IGRT) by helical tomotherapy. METHODS: Twenty-four CRC patients with ≤ 5 metastases were enrolled, receiving a dose of 50 Gy in fractions of 5 Gy. No limitations concerning dimension or localization of the metastases were imposed. Whole body PET-CT was performed at baseline and 3 months after the initiation of RT to evaluate the metabolic response rate according to PET Response Criteria in Solid Tumors (PERCIST) version 1.0. RESULTS: A total of 53 metastases were treated. Seventeen patients (71%) received previously ≥ 1 line of chemotherapy for metastatic disease, displaying residual (n = 7) or progressive (n = 10) metabolic active oligometastatic disease at time of inclusion. Most common sites were the lung, liver and lymphnodes. One patient (4%) experienced grade 3 dysphagia. Twenty-two patients were evaluated by post-treatment PET-CT. Twelve patients achieved a complete (n = 6) or partial (n = 6) metabolic response, resulting in an overall metabolic response rate of 55%. At a median follow-up of 10 months, 7 patients (29%) are in remission, of which 5 received previous chemotherapy with residual oligometastatic disease at time of inclusion. The actuarial 1-year local control, progression-free survival, and overall survival were 54%, 14% and 78%. CONCLUSIONS: Helical tomotherapy delivering 10 fractions of 5 Gy resulted in a metabolic response rate of 55%, and appeared to be attractive as consolidation of inoperable oligometastatic disease after effective chemotherapy. TRIAL REGISTRATION: Eudract 2008-008300-40; NCT00807313.

Phase II study of preoperative helical tomotherapy with a simultaneous integrated boost for rectal cancer.

PURPOSE: The addition of concomitant chemotherapy to preoperative radiotherapy is considered the standard of care for patients with cT3-4 rectal cancer. The combined treatment modality increases the complete response rate and local control (LC), but has no impact on survival or the incidence of distant metastases. In addition, it is associated with considerable toxicity. As an alternative strategy, we explored prospectively, preoperative helical tomotherapy with a simultaneous integrated boost (SIB). METHODS AND MATERIALS: A total of 108 patients were treated with intensity-modulated and image-guided radiotherapy using the Tomotherapy Hi-Art II system. A dose of 46 Gy, in daily fractions of 2 Gy, was delivered to the mesorectum and draining lymph nodes, without concomitant chemotherapy. Patients with an anticipated circumferential resection margin (CRM) of less than 2 mm, based on magnetic resonance imaging, received a SIB to the tumor up to a total dose of 55.2 Gy. Acute and late side effects were scored using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0. RESULTS: A total of 102 patients presented with cT3-4 tumors; 57 patients entered the boost group and 51 the no-boost group. One patient in the no-boost group developed a radio-hypersensitivity reaction, resulting in a complete tumor remission, a Grade 3 acute and Grade 5 late enteritis. No other Grade ≥3 acute toxicities occurred. With a median follow-up of 32 months, Grade ≥3 late gastrointestinal and urinary toxicity were observed in 6% and 4% of the patients, respectively. The actuarial 2-year LC, progression-free survival and overall survival were 98%, 79%, and 93%. CONCLUSIONS: Preoperative helical tomotherapy displays a favorable acute toxicity profile in patients with cT3-4 rectal cancer. A SIB can be safely administered in patients with a narrow CRM and resulted in a promising LC.

Prospective, risk-adapted strategy of stereotactic body radiotherapy for early-stage non-small-cell lung cancer: results of a Phase II trial.

PURPOSE: Validation of a prospective, risk-adapted strategy for early-stage non-small-cell lung cancer (NSCLC) patients treated with stereotactic body radiotherapy (SBRT). METHODS AND MATERIALS: Patients with a T1-3N0M0 (American Joint Committee on Cancer 6th edition) NSCLC were accrued. Using the Radiation Therapy Oncology Group definition, patients were treated to a total dose of 60,Gy in three fractions for peripherally located lesions and four fractions for centrally located lesions. The primary endpoint was toxicity, graded according to the Radiation Therapy Oncology Group acute and late morbidity scoring system, and the National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0. Secondary endpoints were local control and survival. RESULTS: A total of 40 patients were included, 17 with a centrally located lesion. The lung toxicity-free survival estimate at 2 years was 74% and was related to the location (central vs. peripheral) and the size of the target volume. No dose volumetric parameters could predict the occurrence of lung toxicity. One patient died because of treatment-related toxicity. The 1-year and 2-year local progression-free survival estimates were 97% and 84%, respectively, and were related to stage (T1 vs. T2) related (p = 0.006). Local failure was not more frequent for patients treated in four fractions. The 1-year local progression-free survival estimate dropped below 80% for lesions with a diameter of more than 4 cm. CONCLUSION: The proposed risk-adapted strategy for both centrally and peripherally located lesions showed an acceptable toxicity profile while maintaining excellent local control rates. The correlation between local control and tumor diameter calls for the inclusion of tumor stage as a variable in future study design.

Assessment by a deformable registration method of the volumetric and positional changes of target volumes and organs at risk in pharyngo-laryngeal tumors treated with concomitant chemo-radiation.

PURPOSE: Anatomic changes occur during radiation therapy (RT) for head and neck (H&N) tumors. This study aims at quantifying the volumetric and positional changes of gross tumor volumes (GTV), clinical target volumes (CTV), and organs at risk (OAR). Anatomic (CT) and functional (FDG-PET) imaging were used for the delineation of the GTVs. MATERIALS AND METHODS: Ten patients with H&N tumors treated by chemo-RT were used. Contrast-enhanced CT and FDG-PET were acquired prior and during RT following delivery of mean doses of 14.2, 24.5, 35.0, and 44.9 Gy. CT-based GTVs were manually delineated, and PET-based GTVs were segmented using a gradient-based segmentation method. Pre-treatment prophylactic dose CTVs were manually delineated on the pre-treatment CT using consistent and reproducible guidelines. Per-treatment prophylactic CTVs were obtained with an automatic re-contouring method based on deformable registration. For the therapeutic dose CTVs, a 5 mm margin was applied around the corresponding GTVs. OARs such as the parotid glands and the submandibular glands were manually delineated on the pre-treatment CT. OARs on the per-treatment CT were automatically delineated using the method used for prophylactic CTVs. The mean slopes of the relative change in volume over time and the mean displacements of the center of mass after 44.9 Gy were calculated for each volume. RESULTS: Regarding volumetric changes, CT-based and PET-based primary tumor GTVs decreased at a mean rate of 3.2% and 3.9%/treatment day (td), respectively; nodal GTVs decreased at a mean rate of 2.2%/td. This led to a corresponding decrease of the CT-based and PET-based therapeutic CTVs by 2.4% and 2.5%/td, respectively. CT- and PET-based prophylactic tumor CTVs decreased by an average of 0.7% and 0.5%/td, respectively. No difference in volume shrinkage was observed between CT- and PET-based volumes. The ipsilateral and contralateral parotid glands showed a mean decrease of 0.9% and 1.0%/td, respectively. The ipsilateral and contralateral submandibular glands shrank at a mean rate of 1.5% and 1.3%/td, respectively. Regarding positional changes, CT-based GTVs showed a lateral shift of 1.3 mm, PET-based GTVs a posterior shift of 3.4mm and the nodal GTVs a medial shift of 1.0 mm, translating into parallel shifts of the therapeutic CTVs. The ipsilateral prophylactic nodal CTV shifted medially by 1.8 mm. The ipsilateral parotid gland shifted medially by 3.4 mm. The ipsilateral submandibular gland showed a medial shift of 1.7 mm and a superior shift of 2.7 mm. The contralateral submandibular gland only showed a superior shift of 1.7 mm. CONCLUSIONS: Volumetric and positional changes in TVs and OARs were observed during concomitant chemo-RT suggesting that adaptive strategies, where patients are re-imaged and possibly re-planned during treatment, are worth evaluating.

Is (18)F-FDG a surrogate tracer to measure tumor hypoxia? Comparison with the hypoxic tracer (14)C-EF3 in animal tumor models.

INTRODUCTION: Fluorodeoxyglucose (FDG) has been reported as a surrogate tracer to measure tumor hypoxia with positron emission tomography (PET). The hypothesis is that there is an increased uptake of FDG under hypoxic conditions secondary to enhanced glycolysis, compensating the hypoxia-induced loss of cellular energy production. Several studies have already addressed this issue, some with conflicting results. This study aimed to compare the tracers (14)C-EF3 and (18)F-FDG to detect hypoxia in mouse tumor models. MATERIALS AND METHODS: C3H, tumor-bearing mice (FSAII and SCCVII tumors) were injected iv with (14)C-EF3, and 1h later with (18)F-FDG. Using a specifically designed immobilization device with fiducial markers, PET (Mosaic®, Philips) images were acquired 1h after the FDG injection. After imaging, the device containing mouse was frozen, transversally sliced and imaged with autoradiography (AR) (FLA-5100, Fujifilm) to obtain high resolution images of the (18)F-FDG distribution within the tumor area. After a 48-h delay allowing for (18)F decay a second AR was performed to image (14)C-EF3 distribution. AR images were aligned to reconstruct the full 3D tumor volume, and were compared with the PET images. Image segmentation with threshold-based methods was applied on both AR and PET images to derive various tracer activity volumes. The matching index DSI (dice similarity index) was then computed. The comparison was performed under normoxic (ambient air, FSAII: n=4, SCCVII, n=5) and under hypoxic conditions (10% O(2) breathing, SCCVII: n=4). RESULTS: On AR, under both ambient air and hypoxic conditions, there was a decreasing similarity between (14)C-EF3 and FDG with higher activity sub-volumes. Under normoxic conditions, when comparing the 10% of tumor voxels with the highest (18)F-FDG or (14)C-EF3 activity, a DSI of 0.24 and 0.20 was found for FSAII and SCCVII, respectively. Under hypoxic conditions, a DSI of 0.36 was observed for SCCVII tumors. When comparing the (14)C-EF3 distribution in AR with the corresponding (18)F-FDG-PET images, the DSI reached values of 0.26, 0.22 and 0.21 for FSAII and SCCVII under normoxia and SCCVII under hypoxia, respectively. CONCLUSION: This study showed that FDG is not a good surrogate tracer for tumor hypoxia under either ambient or hypoxic conditions. Only specific hypoxia tracers should be used to measure tumor hypoxia.

The limitation of PET imaging for biological adaptive-IMRT assessed in animal models.

PURPOSE: Biological image-guided radiotherapy aims at specifically irradiating biologically relevant sub-volumes within the tumor, as determined for instance by PET imaging. This approach requires that PET imaging be sensitive and specific enough to image various biological pathways of interest, e.g. tumor metabolism, proliferation and hypoxia. In this framework, a validation of PET imaging used for adaptive radiotherapy was undertaken in animal models by comparing small-animal PET images (2.7mm resolution) with autoradiography (AR) (100mum resolution) in various tumors under various physiological situations. METHODS: A specific template for tumor-bearing mouse imaging has been designed (Christian, R&O, 2008). It allows for the registration between MRI images (Biospec, Bruker), FDG-PET images (Mosaic, Philips) and AR (FLA-5100, Fujifilm). After registration, the tumors on the PET and AR images were segmented using a threshold-based method. The thresholds were selected to obtain absolute equal volumes in the PET and AR images. Matching indexes were then calculated between the various volumes. The entire imaging process was performed for FSAII tumors (n=5), SCCVII (n=5) and irradiated (35Gy) FSAII tumors (n=5). RESULTS: In regions with high FDG activity delineated using high value thresholds, low matching values of 39%+/-11% (mean+/-SD) were observed between the volumes delineated on the PET images and those delineated on AR. The matching values progressively increased when considering larger volumes obtained with lower thresholds. These findings were independent of tumor type, tumor metabolism or tumor size. The relationship between the matching values and the percentage of overall tumor volume was fitted through a power regression (r=0.93). As shown by simulations, the matching improved with higher PET resolution. The results can be extrapolated to human tumors imaged with a whole-body PET system. CONCLUSION: Discrepancies were found between the PET images and the underlying microscopic reality represented by AR images. These differences, attributed to the finite resolution of PET, were important when considering small and highly active regions of the tumors. Dose painting based on PET images should therefore be carefully considered and should take these limitations into account.

Alginate moulding: an empirical method for magnetic resonance imaging/positron emission tomography co-registration in a tumor rat model.

BACKGROUND AND PURPOSE: In the experimental field of animal models, co-registration between positron emission tomography (PET) and magnetic resonance imaging (MRI) data still relies on non-automated post-processing using sophisticated algorithms and software developments. We assessed the value of an empirical method using alginate moulding for PET-MR co-registration in a tumor rat model. METHODS: Male WAG/RijHsd rats bearing grafted syngenic rhabdomyosarcoma were examined under general anesthesia by MRI using a clinical whole-body 3-T system equipped with a sensitivity-encoding four-channel wrist coil and by a small animal PET system using labelled [(18)F]-fluorocholine as tracer. An alginate mould including a system of external fiducials was manufactured for each animal, allowing strict immobilization and similar positioning for both modalities. Fourteen rats (27 tumors) had only one MR/PET imaging session. Five rats (9 tumors) had a similar MR/PET session before and 3 days after external radiation therapy (13 Gy in one fraction) using the same mould. Co-registration was performed using the Pmod release 2.75 software (PMOD Technologies, Ltd., Adliswil, Switzerland) with mutual information algorithm. RESULTS: The manufacture of the alginate moulds was easy and innocuous. Imaging sessions were well tolerated. PET-MR co-registration based on mutual information was perfect at visual examination, which was confirmed by the superimposition of external fiducials on fused images. Reuse of the same mould for the post-therapeutic session was feasible 3 days after the pre-therapeutic one in spite of tumor growth. CONCLUSION: The empirical method using alginate moulding with external fiducials for PET-MR co-registration in a rodent tumor model was feasible and accurate.

Immobilization device for in vivo and in vitro multimodality image registration of rodent tumors.

Biological image-guided radiotherapy requires that PET accurately identifies biologically relevant sub-volumes within a tumor. In this framework, an immobilization device was developed to study multi-imaging (CT, micro-MRI, micro-PET, and autoradiography) registration of mouse tumors. The registration accuracy assessed by calculating the average minimal distance between two skew lines was in the order of 0.2-0.3 mm.

Thyroid status is a key modulator of tumor oxygenation: implication for radiation therapy.

In normal tissues, thyroid hormones play a major role in the metabolic activity and oxygen consumption of cells. Because the rate of oxygen consumption is a key factor in the response of tumors to radiation, we hypothesized that thyroid hormones may affect the metabolic activity of tumor cells and hence modulate the response to cytotoxic treatments. We measured the influence of thyroid status on the tumor microenvironment in experimental tumors. Hypothyroidism and hyperthyroidism were generated in mice by chronic treatment with propyl thiouracil and l-thyroxine. Thyroid status significantly modified tumor pO(2) as measured with EPR oximetry. Mechanistically, this was the result of the profound changes in oxygen consumption rates. Thyroid status was associated with a significant change in tumor radiosensitivity since the regrowth delay was increased in hypothyroid mice compared to euthyroid mice, an effect that was abolished when temporarily clamped tumors were irradiated. This study provides unique insights into the impact of modulating tumor oxygen consumption and could have implications in the management of cancer patients with thyroid disorders.

Determination of tumour hypoxia with the PET tracer [18F]EF3: improvement of the tumour-to-background ratio in a mouse tumour model.

PURPOSE: The 2-(2-nitroimidazol-1-yl)-N-(3,3,3-trifluoropropyl)acetamide (EF3) is a 2-nitroimidazole derivative which undergoes bioreductive activation under hypoxic conditions. Using the PET tracer [18F]EF3 in mice, tumour-to-muscle ratios ranging from 1.3 to 3.5 were observed. This study investigated the impact of various interventions aimed at increasing [18F]EF3 elimination, thus potentially increasing the tumour-to-noise ratio in mice, by increasing the renal filtration rate (spironolactone, furosemide), decreasing tubular re-absorption (metronidazole, ornidazole, amino acid solution) or stimulating gastro-intestinal elimination (phenobarbital). METHODS: C3H mice were injected i.v. with an average of 12.95 MBq of [18F]EF3. Drugs were injected i.v. 15 min before the tracer or daily 4 days prior to the experiment (phenobarbital). Anaesthetised mice were imaged from 30 to 300 min with a dedicated animal PET (Mosaic, Philips). Regions of interest were delineated around the tumour, bladder, heart, liver and leg muscle. Radioactivity was expressed as a percentage of injected activity per gram of tissue. RESULTS: Ornidazole decreased the urinary excretion and increased the liver uptake of [18F]EF3, but without causing any changes in the other organs. Phenobarbital significantly increased the liver concentration and decreased radioactivity in blood and muscle without affecting the tracer uptake in tumour. Consequently, a small but non-significant increase in tumour-to-noise ratio was observed. Although some effects were observed with other drugs, they did not modify the tumour-to-noise ratio. CONCLUSION: Only phenobarbital induced a trend toward an increased tumour-to-noise ratio that could possibly be tested in the clinical situation.