Medical Students' Diagnostic Accuracy and Treatment Plans.

Physician-mentored patient rounds (PMPR) were used to assess diagnostic accuracy and treatment plans of preclinical medical students. During 4 PMPR sessions, students gathered patient history, observed a physical exam, analyzed diagnostic tests, and developed treatment plans for a patient with chronic obstructive pulmonary disease. Of 470 students, 99.4% correctly diagnosed the patient. Nearly 78% prescribed long-acting beta-agonists or long-acting muscarinic antagonists. Most included appropriate pharmacologic treatments. Only 47% included smoking cessation in their treatment.

Physician-Mentored Patient Rounds to Observe and Assess Entrustable Professional Activities 1 and 2 in Preclinical Medical Students.

CONTEXT: Thirteen entrustable professional activities (EPAs) for entering residency were created to aid medical educators as they prepare preclinical students for their residency and to assess student readiness for residency. The A.T. Still University Kirksville College of Osteopathic Medicine (ATSU-KCOM) developed a program called physician-mentored patient rounds (PMPR), which focuses on EPA 1 and EPA 2. OBJECTIVE: To determine whether PMPRs could be used to assess expected behaviors of EPA 1 (gather a history and perform a physical examination) and EPA 2 (prioritize a differential diagnosis after a clinical encounter). METHODS: The PMPR sessions at ATSU-KCOM take place over several weeks (30-minute sessions per week), during which students gather a patient's history (sessions 1 and 2), observe a physical examination by the physician mentor (session 2), analyze diagnostic test results (session 3), and formulate a treatment plan (session 4). The PMPRs in this study used a real patient with confirmed chronic obstructive pulmonary disease (COPD). This study did not include the session-4 treatment plan. Between sessions, students completed an assignment to further demonstrate their behaviors as expected in the EPAs. Student responses were analyzed and summarized for physician feedback in the subsequent PMPR session. Students' diagnostic accuracy was measured at the conclusion of each session. RESULTS: A total of 516 students were included in the study. The PMPR weekly attendance was high (453-475). Although history gathering in the large-group setting was disorderly, diagnostic accuracy over the 3-session period improved. After history taking, 411 students (86.5%) included COPD in the differential diagnosis. A smaller number, 235 students (49.5%), listed COPD as the most likely diagnosis. After the physical examination, 439 included COPD in the differential diagnosis, and 385 listed COPD as the most likely diagnosis. After analysis of diagnostic test results, 468 students listed COPD as the most likely diagnosis. CONCLUSION: Physician-mentored patient rounds seem to be an effective means to assess preclinical students' expected behaviors as described in EPA 1 and EPA 2.

Combination of Gold Nanoparticle-Conjugated Tumor Necrosis Factor-α and Radiation Therapy Results in a Synergistic Antitumor Response in Murine Carcinoma Models.

PURPOSE: Although remarkable preclinical antitumor effects have been shown for tumor necrosis factor-α (TNF) alone and combined with radiation, its clinical use has been hindered by systemic dose-limiting toxicities. We investigated the physiological and antitumor effects of radiation therapy combined with the novel nanomedicine CYT-6091, a 27-nm average-diameter polyethylene glycol-TNF-coated gold nanoparticle, which recently passed through phase 1 trials. METHODS AND MATERIALS: The physiologic and antitumor effects of single and fractionated radiation combined with CYT-6091 were studied in the murine 4T1 breast carcinoma and SCCVII head and neck tumor squamous cell carcinoma models. RESULTS: In the 4T1 murine breast tumor model, we observed a significant reduction in the tumor interstitial fluid pressure (IFP) 24 hours after CYT-6091 alone and combined with a radiation dose of 12 Gy (P<.05 vs control). In contrast, radiation alone (12 Gy) had a negligible effect on the IFP. In the SCCVII head and neck tumor model, the baseline IFP was not markedly elevated, and little additional change occurred in the IFP after single-dose radiation or combined therapy (P>.05 vs control) despite extensive vascular damage observed. The IFP reduction in the 4T1 model was also associated with marked vascular damage and extravasation of red blood cells into the tumor interstitium. A sustained reduction in tumor cell density was observed in the combined therapy group compared with all other groups (P<.05). Finally, we observed a more than twofold delay in tumor growth when CYT-6091 was combined with a single 20-Gy radiation dose-notably, irrespective of the treatment sequence. Moreover, when hypofractionated radiation (12 Gy × 3) was applied with CYT-6091 treatment, a more than five-fold growth delay was observed in the combined treatment group of both tumor models and determined to be synergistic. CONCLUSIONS: Our results have demonstrated that TNF-labeled gold nanoparticles combined with single or fractionated high-dose radiation therapy is effective in reducing IFP and tumor growth and shows promise for clinical translation.

Targeting Artificial Tumor Stromal Targets for Molecular Imaging of Tumor Vascular Hypoxia.

Developed and tested for many years, a variety of tumor hypoxia detection methods have been inconsistent in their ability to predict treatment outcomes or monitor treatment efficacy, limiting their present prognostic capability. These variable results might stem from the fact that these approaches are based on inherently wide-ranging global tumor oxygenation levels based on uncertain influences of necrotic regions present in most solid tumors. Here, we have developed a novel non-invasive and specific method for tumor vessel hypoxia detection, as hypoxemia (vascular hypoxia) has been implicated as a key driver of malignant progression, therapy resistance and metastasis. This method is based on high-frequency ultrasound imaging of α-pimonidazole targeted-microbubbles to the exogenously administered hypoxia marker pimonidazole. The degree of tumor vessel hypoxia was assessed in three mouse models of mammary gland carcinoma (4T1, SCK and MMTV-Wnt-1) and amassed up to 20% of the tumor vasculature. In the 4T1 mammary gland carcinoma model, the signal strength of α-pimonidazole targeted-microbubbles was on average 8-fold fold higher in tumors of pimonidazole-injected mice than in non-pimonidazole injected tumor bearing mice or non-targeted microbubbles in pimonidazole-injected tumor bearing mice. Overall, this provides proof of principle for generating and targeting artificial antigens able to be 'created' on-demand under tumor specific microenvironmental conditions, providing translational diagnostic, therapeutic and treatment planning potential in cancer and other hypoxia-associated diseases or conditions.

Dosimetric effect on pediatric conformal treatment plans using dynamic jaw with Tomotherapy HDA.

It is important to minimize the radiation dose delivered to healthy tissues in pediatric cancer treatment because of the risk of secondary malignancies. Tomotherapy HDA provides a dynamic jaw (DJ) delivery mode that creates a sharper penumbra at the craniocaudal ends of a target in addition to a fixed jaw (FJ) delivery mode. The purpose of this study was to evaluate its dosimetric effect on the pediatric cancer cases. We included 6 pediatric cases in this study. The dose profiles and plan statistics­target dose conformity, uniformity, organ-at-risk (OAR) mean dose, beam-on time, and integral dose­were compared for each case. Consequently, the target dose coverage and uniformity were similar for different jaw settings. The OAR dose sparing depended on its relative location to the target and disease sites. For example, in the head and neck cancer cases, the brain stem dose using DJ 2.5 was reduced by more than two-fold (2.4 Gy vs. 6.3 Gy) than that obtained with FJ 2.5. The integral dose with DJ 2.5 decreased by more than 9% compared with that with FJ 2.5. Thus, using dynamic jaw in pediatric cases could be critical to reduce a probability of a secondary malignancy.

Development of a novel multiplexed assay for quantification of transforming growth factor-ß (TGF-ß).

Changes in activity or levels of transforming growth factor-ß (TGF-ß) are associated with a variety of diseases; however, measurement of TGF-ß in biological fluids is highly variable. TGF-ß is biologically inert when associated with its latency-associated peptide (LAP). Most available immunoassays require exogenous activation by acid/heat to release TGF-ß from the latent complex. We developed a novel electrochemiluminescence-based multiplexed assay on the MesoScale Discovery® platform that eliminates artificial activation, simultaneously measures both active TGF-ß1 and LAP1 and includes an internal control for platelet-derived TGF-ß contamination in blood specimens. We optimized this assay to evaluate plasma levels as a function of activation type and clinical specimen preparation. We determined that breast cancer patients' plasma have higher levels of circulating latent TGF-ß (LTGF-ß) as measured by LAP1 than healthy volunteers (p < 0.0001). This assay provides a robust tool for correlative studies of LTGF-ß levels with disease, treatment outcomes and toxicity with a broad clinical applicability.

Merkel Cell Carcinoma: Epidemiology, Target, and Therapy.

Merkel cell carcinoma (MCC) is an aggressive neuroendocrine tumor of the skin with a rising incidence. MCC has metastatic potential regardless the size of the primary tumor and a 5-year disease associated mortality rate is 46 %. Surgery and radiation are the mainstays of management for primary MCC. There is no evidence-based effective chemotherapy for recurrent or metastatic diseases to date. In-depth mechanistic studies in MCC have uncovered important cellular events and the association with a polyomavirus, which has provided direct evidence for molecular targeted and immunotherapy. Further perspective studies and clinical trials are warranted to provide reliable evidence of possible pitfalls and effectiveness of molecular targeted immunotherapy alone or in combination with chemotherapy in MCC.

Long-term results of phase II ablation after breast lumpectomy added to extend intraoperative margins (ABLATE l) trial.

BACKGROUND: Excision followed by radiofrequency ablation (eRFA) is an intraoperative method that uses intracavitary hyperthermia to create an additional tumor-free zone around the lumpectomy cavity in breast cancer patients. We hypothesized that eRFA after lumpectomy for invasive breast cancer could reduce the need for re-excision for close margins as well as potentially maintain local control without the need for radiation. STUDY DESIGN: This prospective phase II institutional review board-approved study was conducted from March 2004 to April 2010. A standard lumpectomy was performed, then the RFA probe was deployed 1 cm circumferentially into the walls of the lumpectomy cavity and maintained at 100 °C for 15 minutes. Validated Doppler sonography was used to intraoperatively determine adequacy of ablation. RESULTS: One hundred patients were accrued to the trial, with an average age of 65.02 years ± 10.0 years. The stages were Tis (n = 30); T1mic (n = 1); T1a (n = 9); T1b (n = 27); T1c (n = 22); T2 (n = 10) ; and T3 (n = 1). Grades were I (n = 48); II (n = 29); and III (n = 23). Seventy-eight subjects had margins >2 mm (negative), 22 patients had margins ≤ 2 mm, of which 12 were close and 3 focally positive, which, at our institution, would have required re-excision (only 1 patient in this group had re-excision). There were 6% postoperative complications, and 24 patients received radiation therapy (XRT). During the study mean follow-up period of 62 months ± 24 months (68-month median follow-up) in patients not treated with XRT, there were 2 in-site tumor recurrences treated with aromitase inhibitor, 3 biopsy entrance site recurrences treated with excision and XRT to conserve the breast, and 2 recurrences elsewhere and 1 contralateral recurrence; all 3 treated with mastectomy. CONCLUSIONS: Long-term follow-up suggests that eRFA may reduce the need for re-excision for close or focally positive margins in breast cancer patients, and eRFA may be a valuable tool for treating favorable patients who desire lumpectomy and either cannot or do not want radiation. A multicenter trial has been initiated based on these results.

Nipple skin-sparing mastectomy is feasible for advanced disease.

BACKGROUND: Skin-sparing mastectomy (SSM) or nipple skin-sparing mastectomy (NSSM) are procedures commonly offered as part of the surgical treatment for breast cancer. Each involves a mastectomy with preservation of the skin overlying the breast (in SSM) and often also the skin overlying the nipple-areolar complex (NSSM). At the time of mastectomy, immediate reconstruction with a tissue expander or implant is performed for a more favorable cosmetic outcome. Until now, these procedures have been reserved for low-risk patients and are rarely offered to patients with advanced disease where neoadjuvant chemotherapy and postmastectomy radiation are a planned part of the treatment. We report our experience of SSM and NSSM in such high-risk patients. METHODS: This retrospective study from 2001 to 2012 evaluates the outcomes of 527 patients who underwent SSM or NSSM. Sixty patients with advanced disease who underwent neoadjuvant chemotherapy followed by SSM or NSSM with immediate reconstruction and subsequent radiotherapy (RT) were identified. The cosmetic and oncologic outcomes of this patient group were noted. RESULTS: A total of 527 patients in our study group had a total of 1,035 skin-sparing mastectomies (558 NSSM and 477 SSM; 444 patients with bilateral and 83 with unilateral procedures). Of the 60 patients with locally advanced disease, 39 underwent NSSM and 21 underwent SSM. All patients received RT to the diseased side. Mean age of the group was 50.2 ± 10.8 years, with a range of 27-75 years for NSSM and 29-73 years for SSM. The lymph node status was positive in 71.8 % with an average tumor size of 3.8 ± 2.5 cm. The overall radiation-induced complication rate was 38.1 % (8 of 21) in the SSM group and 30.8 % (12 of 39) in the NSSM group. Wound infections and tissue necrosis occurred at a rate of 16.7 %. The implant was removed in 5 % of these cases. Capsular contracture occurred at a rate of 10.2 %. Radiation-related nonbreast complications occurred in 6.7 % of the cases. Examples of these radiation-related nonbreast complications included radiation pneumonitis, stenosis of the superior vena cava requiring venoplasty and severe atypical chest pain thought to be consistent with osteochondritis. The locoregional recurrence rate (median follow-up of 18 months) was 14.3 % (3 of 21) in the SSM group and 10.3 % (4 of 39) in the NSSM group. CONCLUSIONS: SSM and NSSM have been offered to patients with relatively low-risk breast cancer as oncologically safe while affording superior cosmesis with one-step immediate reconstruction. Our series demonstrates that either procedure can be offered to patients with more advanced cancers requiring postoperative RT. The complication rates are comparable to those reported for patients undergoing RT after traditional mastectomies.

Combining stereotactic radiosurgery and systemic therapy for brain metastases: a potential role for temozolomide.

Brain metastases are unfortunately very common in the natural history of many solid tumors and remain a life-threatening condition, associated with a dismal prognosis, despite many clinical trials aimed at improving outcomes. Radiation therapy options for brain metastases include whole brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS). SRS avoids the potential toxicities of WBRT and is associated with excellent local control (LC) rates. However, distant intracranial failure following SRS remains a problem, suggesting that untreated intracranial micrometastatic disease is responsible for failure of treatment. The oral alkylating agent temozolomide (TMZ), which has demonstrated efficacy in primary malignant central nervous system tumors such as glioblastoma, has been used in early phase trials in the treatment of established brain metastases. Although results of these studies in established, macroscopic metastatic disease have been modest at best, there is clinical and preclinical data to suggest that TMZ is more efficacious at treating and controlling clinically undetectable intracranial micrometastatic disease. We review the available data for the primary management of brain metastases with SRS, as well as the use of TMZ in treating established brain metastases and undetectable micrometastatic disease, and suggest the role for a clinical trial with the aims of treating macroscopically visible brain metastases with SRS combined with TMZ to address microscopic, undetectable disease.

Mechanisms of glioma-associated neovascularization.

Glioblastomas (GBMs), the most common primary brain tumor in adults, are characterized by resistance to chemotherapy and radiotherapy. One of the defining characteristics of GBM is an abundant and aberrant vasculature. The processes of vascular co-option, angiogenesis, and vasculogenesis in gliomas have been extensively described. Recently, however, it has become clear that these three processes are not the only mechanisms by which neovascularization occurs in gliomas. Furthermore, it seems that these processes interact extensively, with potential overlap among them. At least five mechanisms by which gliomas achieve neovascularization have been described: vascular co-option, angiogenesis, vasculogenesis, vascular mimicry, and (the most recently described) glioblastoma-endothelial cell transdifferentiation. We review these mechanisms in glioma neovascularization, with a particular emphasis on the roles of hypoxia and glioma stem cells in each process. Although some of these processes are well established, others have been identified only recently and will need to be further investigated for complete validation. We also review strategies to target glioma neovascularization and the development of resistance to these therapeutic strategies. Finally, we describe how these complex processes interlink and overlap. A thorough understanding of the contributing molecular processes that control the five modalities reviewed here should help resolve the treatment resistance that characterizes GBMs.

Resistance of glioblastoma-initiating cells to radiation mediated by the tumor microenvironment can be abolished by inhibiting transforming growth factor-ß.

The poor prognosis of glioblastoma (GBM) routinely treated with ionizing radiation (IR) has been attributed to the relative radioresistance of glioma-initiating cells (GIC). Other studies indicate that although GIC are sensitive, the response is mediated by undefined factors in the microenvironment. GBM produce abundant transforming growth factor-ß (TGF-ß), a pleotropic cytokine that promotes effective DNA damage response. Consistent with this, radiation sensitivity, as measured by clonogenic assay of cultured murine (GL261) and human (U251, U87MG) glioma cell lines, increased by approximately 25% when treated with LY364947, a small-molecule inhibitor of TGF-ß type I receptor kinase, before irradiation. Mice bearing GL261 flank tumors treated with 1D11, a pan-isoform TGF-ß neutralizing antibody, exhibited significantly increased tumor growth delay following IR. GL261 neurosphere cultures were used to evaluate GIC. LY364947 had no effect on the primary or secondary neurosphere-forming capacity. IR decreased primary neurosphere formation by 28%, but did not reduce secondary neurosphere formation. In contrast, LY364947 treatment before IR decreased primary neurosphere formation by 75% and secondary neurosphere formation by 68%. Notably, GL261 neurospheres produced 3.7-fold more TGF-ß per cell compared with conventional culture, suggesting that TGF-ß production by GIC promotes effective DNA damage response and self-renewal, which creates microenvironment-mediated resistance. Consistent with this, LY364947 treatment in irradiated GL261 neurosphere-derived cells decreased DNA damage responses, H2AX and p53 phosphorylation, and induction of self-renewal signals, Notch1 and CXCR4. These data motivate the use of TGF-ß inhibitors with radiation to improve therapeutic response in patients with GBM.

Prone hypofractionated whole-breast radiotherapy without a boost to the tumor bed: comparable toxicity of IMRT versus a 3D conformal technique.

PURPOSE: We report a comparison of the dosimetry and toxicity of three-dimensional conformal radiotherapy (3D-CRT) vs. intensity-modulated radiotherapy (IMRT) among patients treated in the prone position with the same fractionation and target of the hypofractionation arm of the Canadian/Whelan trial. METHODS AND MATERIALS: An institutional review board-approved protocol identified a consecutive series of early-stage breast cancer patients treated according to the Canadian hypofractionation regimen but in the prone position. Patients underwent IMRT treatment planning and treatment if the insurance carrier approved reimbursement for IMRT; in case of refusal, a 3D-CRT plan was used. A comparison of the dosimetric and toxicity outcomes during the acute, subacute, and long-term follow-up of the two treatment groups is reported. RESULTS: We included 97 consecutive patients with 100 treatment plans in this study (3 patients with bilateral breast cancer); 40 patients were treated with 3D-CRT and 57 with IMRT. IMRT significantly reduced the maximum dose (Dmax median, 109.96% for 3D-CRT vs. 107.28% for IMRT; p < 0.0001, Wilcoxon test) and improved median dose homogeneity (median, 1.15 for 3D-CRT vs. 1.05 for IMRT; p < 0.0001, Wilcoxon test) when compared with 3D-CRT. Acute toxicity consisted primarily of Grade 1 to 2 dermatitis and occurred in 92% of patients. Grade 2 dermatitis occurred in 13% of patients in the 3D-CRT group and 2% in the IMRT group. IMRT moderately decreased rates of acute pruritus (p = 0.03, chi-square test) and Grade 2 to 3 subacute hyperpigmentation (p = 0.01, Fisher exact test). With a minimum of 6 months' follow-up, the treatment was similarly well tolerated in either group, including among women with large breast volumes. CONCLUSION: Hypofractionated breast radiotherapy is well tolerated when treating patients in the prone position, even among those with large breast volumes. Breast IMRT significantly improves dosimetry but yields only a modest but confirmed benefit in terms of toxicities. If a concurrent boost to the tumor bed is not required, a conformal 3D-CRT approach can adequately deliver prone whole-breast hypofractionation radiotherapy.

Management of high-risk localized prostate cancer.

Traditionally, patients with high-risk localized prostate cancer have been an extremely challenging group to manage due to a significant likelihood of treatment failure and prostate cancer-specific mortality (PCSM). The results of multiple large, prospective, randomized trials have demonstrated that men with high-risk features who are treated in a multimodal fashion at the time of initial diagnosis have improved overall survival. Advances in local treatments such as dose-escalated radiotherapy in conjunction with androgen suppression and postprostatectomy adjuvant radiotherapy have also demonstrated benefits to this subset of patients. However, therapeutic enhancement with the addition of chemotherapy to the primary treatment regimen may help achieve optimal disease control.

Squamous cell carcinoma of the prostate.

Squamous cell carcinoma of the prostate is a rare tumor, making up 0.5% to 1% of all prostate carcinomas. It is typically described as an aggressive cancer, with a median postdiagnosis survival of 14 months. Presented here is a case of primary squamous cell carcinoma of the prostate, with a complicated presentation of metastatic disease. Due to the extent of the patient's disease, he was treated with palliative radiation therapy using a four-field technique (AP/PA and left and right lateral fields) with 18 mV photons prescribed to the 100% isodose line. The prescription dose was 4000 cGy in 16 fractions of 250 cGy per fraction. No definitive treatment of squamous cell carcinoma of the prostate exists but varying approaches including surgical intervention, chemotherapy, and radiation therapy have been implemented without durable response. However, multimodal treatments appear to be the most promising with longer durations of survival.

Review of chemoradiotherapy for high-risk prostate cancer.

While most newly-diagnosed prostate cancers are well-differentiated tumors that have high probability of cure, there is a subset of patients that present with aggressive malignancies that have significant potential for recurrence and metastasis. Single-modality treatment approaches have demonstrated relatively high failure rates, and multimodality therapy (radiation therapy and hormonal ablation therapy) has become standard of care for these patients. These treatments are not without toxicity, and a significant percentage of patients will become refractory to hormonal therapy. Historically, radiation therapy of prostate cancer was associated with significant genitourinary and gastrointestinal morbidity. With advances in radiation therapy techniques and delivery, the potential for safe dose-escalation has emerged. Further, there is an opportunity for chemotherapeutic agents to play an important syngergistic role in radiosensitizing the tumor cells at the primary site while also addressing micrometastatic disease. Concurrent chemoradiation therapy has become standard treatment for many types of locally advanced tumors, including lung, cervical, esophageal, rectal, and anal malignancies. We present a review of clinical trials examining the role of chemoradiation therapy in high-risk prostate cancer.

Novel imaging provides new insights into mechanisms of oxygen transport in tumors.

Hypoxia is a common feature of solid tumors, and abnormal tumor oxygen transport is a key factor in the imbalance between tumor oxygen supply and demand. Novel advanced imaging techniques can enable new insights into the complexities of tumor oxygen transport and hypoxia that were not previously known or fully appreciated. In this paper, we document new insights into tumor oxygen transport enabled by spectral imaging of microvascular hemoglobin saturation.

Her2/neu signaling blockade improves tumor oxygenation in a multifactorial fashion in Her2/neu+ tumors.

PURPOSE: Tumor hypoxia reduces the efficacy of radiation and chemotherapy as well as altering gene expression that promotes cell survival and metastasis. The growth factor receptor, Her2/neu, is overexpressed in 25-30% of breast tumors. Tumors that are Her2(+) may have an altered state of oxygenation, relative to Her2(-) tumors, due to differences in tumor growth rate and angiogenesis. METHODS: Her2 blockade was accomplished using an antibody to the receptor (trastuzumab; Herceptin). This study examined the effects of Her2 blockade on tumor angiogenesis, vascular architecture, and hypoxia in Her2(+) and Her2(-) MCF7 xenograft tumors. RESULTS: Treatment with trastuzumab in Her2(+) tumors significantly improved tumor oxygenation, increased microvessel density, and improved vascular architecture compared with the control-treated Her2(+) tumors. The Her2(+) xenografts treated with trastuzumab also demonstrated decreased proliferation indices when compared with control-treated xenografts. These results indicate that Her2 blockade can improve tumor oxygenation by decreasing oxygen consumption (reducing tumor cell proliferation and inducing necrosis) and increasing oxygen delivery (vascular density and architecture). CONCLUSIONS: These results support the use of trastuzumab as an adjunct in the treatment of breast tumors with chemotherapy or radiotherapy, as improvements in tumor oxygenation should translate into improved treatment response.

Spectral imaging facilitates visualization and measurements of unstable and abnormal microvascular oxygen transport in tumors.

Abnormal microvasculature contributes to the pathophysiologic microenvironment of tumors. Understanding microvascular tumor oxygen transport is necessary to comprehend the factors that influence tumor biology, physiology, and therapy. Previously, we described an in vivo spectral imaging microscopy system for measurements of microvessel hemoglobin saturation (HbSat). We measure temporal fluctuations and spatial gradients in tumor microvessel oxygenation and identify instances of anastomoses between vessels with significantly different oxygenations. Slow periodic fluctuations in HbSat <0.2 cycles per minute were observed. These measurements are consistent with microelectrode measurements of fluctuating tumor oxygenation. Gradients in HbSat along individual tumor microvessels were measured that were larger in magnitude than normal tissue microvessels. Images were captured of anastomoses of tumor microvessels with diameters 20%). Shunting of inspired oxygen, presumably due to arteriovenous anastomoses, from tumor feeding arterioles to adjacent venules was imaged. This effect was confined to a region around the tumor and was not observed in nearby normal microvessels. Imaging measurements of tumor microvessel oxygen transport may offer insight to current questions regarding oxygen-related tumor biology and treatment responses, and spectral imaging may be a useful research tool in this regard.