Introduction to Exceptional Response

What is/are Exceptional Response?

Exceptional Response - This exceptional response of pancreatic TB to conservative management makes it imperative that the condition be diagnosed promptly to avoid any futile surgical interventions and associated complications. ^[1] We present the first case of breast metastasis (BM) from a UC described in literature who had an exceptional response to second-line therapy with pembrolizumab in association with radiotherapy, showing the efficacy of combining immunotherapy and radiotherapy even in patients with atypical metastatic sites. ^[2] Given the rarity of patients with exceptional responses to targeted agents, cooperative efforts to understand the molecular basis for these phenotypes are essential. ^[3] The exceptional response seen in a patient with CD74‐NRG1‐rearranged NSCLC suggests further exploration in NRG1‐fusion–positive cancers. ^[4] Recent clinical trials have shown that intensifying anti-androgen therapies administered before prostatectomy can induce pathologic complete responses or minimal residual disease, called exceptional response, although the molecular determinants of these clinical outcomes are largely unknown. ^[5] This case highlights an exceptional response of skeletal metastases to 177LuPSMA that is undermined by neuroendocrine transformation in the liver. ^[6] report that mechanisms of exceptional response to cancer treatment can be grouped into four broad categories: dysregulated intracellular signaling pathways, altered DNA damage response, tumor microenvironment or immune engagement, and alterations associated with a favorable prognosis. ^[7] Background Late-stage cancer immunotherapy trials strive to demonstrate the clinical efficacy of novel immunotherapies, which is leading to exceptional responses and long-term survival in subsets of patients. ^[8] The use of TRK inhibitors in salivary secretory carcinoma has led to exceptional responses. ^[9] Here we describe the case of a patient with chemo-refractory advanced PDAC with an activating exon-19 EGFR mutation who had an exceptional response to erlotinib monotherapy. ^[10] Twelve patients (40% of responders) experienced exceptional responses lasting three times longer than expected for their respective disease. ^[11] The exceptional response to immune checkpoint inhibitor in the first reported case highlights the potential clinical importance of identifying tumors with DEK-AFF2 fusions. ^[12] A novel DEK-AFF2 fusion was recently reported in 4 nonkeratinizing squamous cell carcinomas of the sinonasal region and skull base, including 1 with exceptional response to immunotherapy, but it is not yet clear if this rearrangement defines a unique clinicopathologic category or represents a rare event. ^[13] Recent clinical trials have shown that intensifying anti-androgen therapies administered prior to prostatectomy can induce pathologic complete responses (pCR) or minimal residual disease (MRD) (<5 mm), together termed exceptional response, although the molecular determinants of these clinical outcomes are largely unknown. ^[14] Clinical samples were obtained from breast cancer patients who showed exceptional responses to anti-HER2 therapy or hormonal therapy and from those who did not. ^[15] Identification of patients with exceptional responses in MSS CRC and predictive biomarkers is an unmet need that needs to be addressed. ^[16] Therefore, we started carboplatin chemotherapy which resulted in an exceptional response regarding biochemical, radiographic parameters accompanied by significant improvement of patients' physical condition. ^[17] In a cohort of metastatic melanoma survivors with exceptional responses to immunotherapy, we probed memory CD8+ T-cell responses across tissues, and across several years. ^[18] This was an exceptional response situation and the lessons learned are applicable to other landslide disaster crises. ^[19] We report the case of a 68-year-old man with ATM mutation-positive mCRPC who showed exceptional response to concomitant administration of enzalutamide with 177Lu-PSMA-617. ^[20] CONCLUSION Given the lack of data informing on optimal management of INI1-deficient pancreatic undifferentiated rhabdoid carcinoma, and the exceptional response achieved by gemcitabine with nab-paclitaxel, this case report highlights a surprising and potentially informative anecdote. ^[21] Often touted are the exceptional response rates in heavily pretreated patients along with meaningful durability of response and ultimately progressionfree survival that were found in the ZUMA-1 and JULIET studies for axicabtagene ciloleucel (axicel, Yescarta) and tisagenlecleucel (tisa-cel, Kymriah), respectively (Neelapu et al. ^[22] One characteristic of the digital age is that attention is not only scarce and increasingly contested but also continuously measured and compared, leading to a heightened value around everything that seems to draw an exceptional response. ^[23] • The unexpected response to checkpoint inhibitors could be explained by a very high affinity of the fusion peptide at the junction of BRD4 and NUT to the MHC complex as recently suggested for an exceptional response to an immune checkpoint inhibitor in a fusion bearing low TMB, low PD-L1 expression head and neck carcinoma. ^[24] Precision medicine in oncology leverages clinical observations of exceptional response. ^[25] While the majority of patients responds to PSMA-RLT, with 10-15% having an exceptional response, approximately 30% of patients is unresponsive to PSMA-RLT. ^[26] The mechanism of action for exceptional response was elucidated by in vitro experiments that demonstrated that the fact that tamoxifen can have an agonistic effect in addition to antagonist activity, whereas letrozole results only in estrogen depletion was crucial to the response achieved when letrozole was combined with an MEK inhibitor. ^[27] Using a 1 x 1 x 1 design, we rapidly identify tumors with exceptional responses to combination treatments. ^[28] It argues, first, that the prominent (counter-)terrorism paradigm – in which terrorism is approached as a ubiquitous and very specific security challenge meriting appropriately exceptional responses – is far more critiqued than we might anticipate. ^[29] Purpose: We sought to determine the mechanism of an exceptional response in a patient diagnosed with a SMARCB1/INI1-negative chordoma treated with tazemetostat, an EZH2 inhibitor, and followed by radiotherapy. ^[30] Medical record review revealed two patients with HNFS AS received off-label treatment with anti-PD-1 therapy and experienced exceptional responses, highlighting immune checkpoint inhibition as a therapeutic avenue for HNFS AS. ^[31] Here we examine the landscape of TMB and PD-L1 expression in breast cancer and present a case of patient with high TMB and PD-L1 negative breast cancer with exceptional response to ICPIs. ^[32] The case exhibited an exceptional response to cryoablation followed by pembrolizumab, potentially attributed to mutations in POLE, which lead to an extremely high TMB. ^[33] To the Editor: We report an exceptional case of a patient with Tlymphoblastic lymphoma (T-LBL) with a chromosomal translocation resulting in a platelet-derived growth factor receptor beta (PDGFRB) rearrangement who relapsed after receiving standard conventional chemotherapy but subsequently had an exceptional response to single agent tyrosine kinase inhibition. ^[34] Three patients with nonmuscle invasive bladder cancer [1 patient with an exceptional response; complete response (CR) for 30 months] who failed intravesical BCG were evaluated using an NYS CLEP approved assay, Immune Report Card, which measures programmed death-ligand 1 expression, CD8+ T-cell infiltration pattern, mutational burden, and gene expression of 51 immune-related transcripts using RNA-Seq. ^[35] Subgroup analyses of CheckMate 214 revealed exceptional response in patients with sarcomatoid histology. ^[36] Areas covered: This review provides select examples of exceptional response analyses and the ramifications of these analyses upon biomarker selection and clinical trial design within the context of precision medicine. ^[37] We describe an exceptional response to single agent nivolumab postradiation therapy in a 13-year-old adolescent with poorly differentiated cervical carcinoma and widespread metastatic disease. ^[38] Here, we report a patient with wide spread uveal melanoma who had an exceptional response to treatment with ipilimumab and nivolumab, but suffered severe immune-related sequelae, including central serous retinopathy with retinal detachment, tinnitus, and vitiligo resembling Vogt-Koyanagi-Harada disease, and refractory enteritis. ^[39] We report an exceptional response in a 75-year-old patient withmCRPCwho underwent 16 cycles of Lu-PSMAunder a compassionate use programme over 50months that included the initial treatment and three rechallenge series, each comprising four RLTcycles. ^[40] We hypothesize that survival or patients with an exceptional response may be predicted based on clinical factors. ^[41] The exceptional response has always been the most intriguing part of the clinical practice of medicine. ^[42] Several patients exhibited exceptional response with residual tumor burdens less than 0. ^[43] This exceptional response is linked to the presence of intrinsic defects in the yellowish particles and, hence, the specific conditions of the proposed methodology become crucial to produce a propitious TiO2-defective nanomaterial capable of photo-degrade the phenol molecule, in contrast with the lack of photocatalytic activity currently exhibited by commercial photocatalysts under visible light. ^[44] Exceptional responses to bortezomib can be achieved in KRAS G12D-mutant NSCLCs. ^[45] We report the case of a patient with a Siewert class III gastroesophageal junction squamous carcinoma with metastatic spread into the liver who had an exceptional response to a combination therapy of nivolumab and ipilimumab despite being programmed death-ligand 1 (PD-L1) negative, microsatellite stable (MSS), and having a low tumor mutational burden. ^[46] Concurrently, efforts to identify molecular alterations in tumors that exhibited exceptional response after systemic treatment with standard or investigational agents have been published or are in progress. ^[47] Exceptional responses to crizotinib in breast cancer patients with somatic MET and ROS1 alterations [abstract]. ^[48] Our investigation of genome-wide CNA burden offers the potential to gain insight into the underlying genetic landscape of long-term, never relapse exceptional response to trastuzumab. ^[49] We report a case of a 67-year-old man with pazopanib-resistant metastatic renal cell carcinoma (mRCC) who showed an exceptional response to everolimus. ^[50]

Experienced Exceptional Response

Twelve patients (40% of responders) experienced exceptional responses lasting three times longer than expected for their respective disease. ^[1] Medical record review revealed two patients with HNFS AS received off-label treatment with anti-PD-1 therapy and experienced exceptional responses, highlighting immune checkpoint inhibition as a therapeutic avenue for HNFS AS. ^[2]

Exhibited Exceptional Response

Several patients exhibited exceptional response with residual tumor burdens less than 0. ^[1] Concurrently, efforts to identify molecular alterations in tumors that exhibited exceptional response after systemic treatment with standard or investigational agents have been published or are