Impact of nodal status and tumor burden in sentinel lymph nodes on the clinical outcomes of cancer patients

Leong, Stanley P. L.; Zuber, Markus; Ferris, Robert L.; Kitagawa, Yuko; Cabanas, Ramon M.; Levenback, Charles; Faries, Mark B.; Saha, Sukamal

doi:10.1002/jso.21815

Cited by 38 publications

(36 citation statements)

References 159 publications

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“…3). However, since LNs are one main source of tumor spread and metastases (summarized in [79]), a case-by-case decision regarding the length of time that a diseased LN should remain in the patient's body would have to be made by the clinical team. Very recently, Burnette and colleagues have demonstrated that RT drastically enhances the number and cross-priming capacity of tumor-infiltrating CD11b + /Ly-6C + /MHC class II + DCs in a type I interferon-dependent manner [80].…”

Section: Radiotherapy and Immune Activationmentioning

confidence: 99%

Induction of Abscopal Anti-Tumor Immunity and Immunogenic Tumor Cell Death by Ionizing Irradiation - Implications for Cancer Therapies

Frey¹,

Rubner²,

Wunderlich³

et al. 2012

CMC

126

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Although cancer progression is primarily driven by the expansion of tumor cells, the tumor microenvironment and anti-tumor immunity also play important roles. Herein, we consider how tumors can become established by escaping immune surveillance and also how cancer cells can be rendered visible to the immune system by standard therapies such as radiotherapy or chemotherapy, either alone or in combination with additional immune stimulators. Although local radiotherapy results in DNA damage (targeted effects), it is also capable of inducing immunogenic forms of tumor cell death which are associated with a release of immune activating danger signals (non-targeted effects), such as necrosis. Necrotic tumor cells may result from continued exposure to death stimuli and/or an impaired phosphatidylserine (PS) dependent clearance of the dying tumor cells. In such circumstances, mature dendritic cells take up tumor antigen and mediate the induction of adaptive and innate anti-tumor immunity. Locally-triggered, systemic immune activation can also lead to a spontaneous regression of tumors or metastases that are outside the radiation field - an effect which is termed abscopal. Preclinical studies have demonstrated that combining radiotherapy with immune stimulation can induce anti-tumor immunity. Given that it takes time for immunity to develop following exposure to immunogenic tumor cells, we propose practical combination therapies that should be considered as a basis for future research and clinical practice. It is essential that radiation oncologists become more aware of the importance of the immune system to the success of cancer therapy.

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Section: Radiotherapy and Immune Activationmentioning

confidence: 99%

Induction of Abscopal Anti-Tumor Immunity and Immunogenic Tumor Cell Death by Ionizing Irradiation - Implications for Cancer Therapies

Frey¹,

Rubner²,

Wunderlich³

et al. 2012

CMC

126

View full text Add to dashboard Cite

show abstract

“…These may eclipse both PD1 and CTLA-4, and our decade old therapy IL-2, but it's the tumor infiltration that may be a biomarker of very great relevance to all of these outcomes. This whole conference on nodal disease began with Stanley Leong's clairvoyant realization that the node is the turnstile through which this tumor travels in the majority of patients [138]. We have ignored the lymph node—(not the surgeons here, but many outside of the surgical community) have ignored the node despite performing sentinel node biopsy upon hundreds of patients each year.…”

Section: Discussant Summary and Commentmentioning

confidence: 99%

Progression of cutaneous melanoma: implications for treatment

Leong

Mihm

Murphy

et al. 2012

Clin Exp Metastasis

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The survival rates of melanoma, like any type of cancer, become worse with advancing stage. Spectrum theory is most consistent with the progression of melanoma from the primary site to the in-transit locations, regional or sentinel lymph nodes and beyond to the distant sites. Therefore, early diagnosis and surgical treatment before its spread is the most effective treatment. Recently, new approaches have revolutionized the diagnosis and treatment of melanoma. Genomic profiling and sequencing will form the basis for molecular taxonomy for more accurate subgrouping of melanoma patients in the future. New insights of molecular mechanisms of metastasis are summarized in this review article. Sentinel lymph node biopsy has become a standard of care for staging primary melanoma without the need for a more morbid complete regional lymph node dissection. With recent developments in molecular biology and genomics, novel molecular targeted therapy is being developed through clinical trials.

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“…1 In addition to tumor size, lymph node status (positive/negative lymph node metastasis) is regarded as the strongest prognostic factor for patient's cancer-specific survival. 2,3 It is widely used for guiding therapeutic decisions and currently justifies a systematic lymphadenectomy in early cervical cancer.…”

mentioning

confidence: 99%

Improved computer-assisted analysis of the global lymphatic network in human cervical tissues

et al. 2014

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Lymphatic dissemination is a key event in cervical cancer progression and related tumor lymphatic markers are viewed as promising prognostic factor of nodal extension. However, validating such parameters requires an objective characterization of the lymphatic vasculature. Here, we performed a global analysis of the lymphatic network using a new computerized method applied on whole uterine cervical digital images. Sixty-eight cases of cervical neoplasia (12 CIN3, 10 FIGO stage 1A and 46 stage IB1) and 10 cases of normal cervical tissue were reacted with antibodies raised against D2-40, D2-40/p16 and D2-40/Ki67. Immunostained structures were automatically detected on whole slides. The lymphatic vessel density (D2-40), proliferating lymphatic vessel density (D2-40/ki67) and spatial lymphatic distribution in respect to the adjacent epithelium were assessed from normal cervix to early cervical cancer and correlated with lymphovascular space invasion and lymph node status. Prominent lymphatic vessel density and proliferating lymphatic vessel density are detected under the transformation zone of benign cervix and no further increase is noted during cancer progression. Notably, a shift of lymphatic vessel distribution toward the neoplastic edges is detected. In IB1 cervical cancer, although intra-and peritumoral lymphatic vessel density are neither correlated with lymphovascular space invasion nor with lymph node metastasis, a specific spatial distribution with more lymphatic vessels in the vicinity of tumor edges is predictive of lymphatic dissemination. Herein, we provide a new computerized method suitable for an innovative detailed analysis of the lymphatic network. We show that the transformation zone of the benign cervix acts as a baseline lymphangiogenic niche before the initiation of neoplastic process. During cancer progression, this specific microenvironment is maintained with lymphatic vessels even in closer vicinity to tumor cells.

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Impact of nodal status and tumor burden in sentinel lymph nodes on the clinical outcomes of cancer patients

Cited by 38 publications

References 159 publications

Induction of Abscopal Anti-Tumor Immunity and Immunogenic Tumor Cell Death by Ionizing Irradiation - Implications for Cancer Therapies

Induction of Abscopal Anti-Tumor Immunity and Immunogenic Tumor Cell Death by Ionizing Irradiation - Implications for Cancer Therapies

Progression of cutaneous melanoma: implications for treatment

Improved computer-assisted analysis of the global lymphatic network in human cervical tissues

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