Management Of Residual Disease Research Articles

Management of Fibrous Hamartoma of Infancy: A Contemporary Series

BackgroundFibrous hamartoma of infancy (FHI) is a rare, benign, soft tissue mass that may be locally infiltrative. Primary excision is the mainstay of treatment; however, given the infiltrative nature, margin negativity can be difficult to achieve. The management of residual disease in the setting of positive margins after primary excision is not well described. MethodsAll patients undergoing FHI excision from 2012 to 2022 were included. Demographics, operative data, margin status, recurrence, and post-operative follow-up data were obtained via retrospective chart review. ResultsNine patients were identified who underwent FHI excision. The median age at time of excision was 9 months (IQR 16). Seven (78%) were male, and the majority (78%) were white. Seven (78%) underwent preoperative imaging via ultrasound or MRI, and 4 (44%) had a preoperative biopsy to confirm diagnosis. Common locations included upper extremity (n = 4, 44%) and lower extremity/inguinal region (n = 4, 44%). Six patients (67%) had positive margins on pathology – 3 (33%) on the upper extremity, 2 (22%) on the lower extremity/inguinal region, and one (11%) on the flank. One patient (11%) had a local recurrence which did not undergo re-excision. ConclusionsFHI remains a rare diagnosis. There is a high margin positivity rate; however, local clinically significant mass recurrence remains uncommon. With low rates of clinically significant mass development coupled with the benign nature of disease, a “watch and wait” approach may be appropriate for patients with positive histologic margins after complete gross excision to avoid reoperation and need for complex reconstructions. Level of EvidenceLevel 4.

Targeted Axillary Dissection: A Review Covering Technical Aspects, Current Recommendations and the Future

For clinically node positive patients with breast cancer, traditionally the gold standard for management of the axilla has been axillary lymph node dissection. This however has been associated with a high rate of morbidity including lymphoedema and shoulder stiffness. With the introduction of neo-adjuvant systemic therapy many patients undergo pathological complete response within the breast and axilla, particularly in certain molecular subtypes of breast cancer propelling interest in de-escalation surgery to reduce this morbidity. Targeted axillary dissection is a procedure combining targeted lymph node biopsy, removing a previously marked node with confirmed cancer prior to neo-adjuvant systemic therapy and sentinel lymph node biopsy. The aim of the procedure is to accurately re-stage the axilla in patients with known nodal metastases after systemic therapy and reduce the morbidity associated with axillary dissection. Current meta-analyses have demonstrated that performing targeted axillary clearance has a consistently lower false negative rate when re-staging the axilla compared to sentinel or targeted node biopsy alone. This has led to a huge increase in popularity for the procedure. However, long-term data for oncological outcomes and morbidity are still lacking. This review article aims to provides an overview of targeted axillary dissection. Focusing on technical aspects, including clip selection, number of clipped nodes and localization techniques for identifying the clipped node prior to surgery. The improved false negative rates of targeted lymph node dissection compared to sentinel node biopsy in clinically node positive patients converting to clinically node negative patients after neo-adjuvant systemic therapy. Pathological and radiological factors that may help in predicting nodal response to neo-adjuvant systemic therapy. Current guidelines/ recommendations for patient selection and management of residual disease within the axilla based on limited data and future studies aiming to clarify treatment decisions for this group of patients.

Standard versus high-dose chemotherapy in mediastinal germ cell tumors: a narrative review.

The aim of this review is to analyze feasibility and toxicities of high-dose chemotherapy (HDCT) in comparison to standard dose chemotherapy (SDCT) in patients affected by mediastinal germ cell tumors (MGCTs), discussing factors that may affect therapeutic choices, such as: management of residual disease, early response predictors for chemotherapeutic efficacy and determinants of chemotherapeutic resistance. In this review, we discuss the main clinical experiences with HDCT and SDCT in germ cell tumor (GCT) patients specifically in those affected by MGCT. MGCTs represent a very small subset characterized by a poor prognosis, despite improvements in their clinical management and in understanding their biology. From early 1970s, HDCT has become an alternative to SDCT for both first-line and salvage therapeutic settings in advanced GCT patients. Several HDCT schedules-either cisplatin or carboplatin-based-have been tested so far, both in clinical randomized trial and in single-center experiences, with divergent results in terms of clinical outcomes and tolerability. Moreover, the majority of these studies included, but were not exclusively designed for, advanced MGCT patients, making difficult to infer data for this specific subset. an extended review of literature through PubMed was conducted using the keywords "mediastinal germinal cell tumors", "standard dose chemotherapy" and "high dose chemotherapy". HDCT regimens could not be considered to date a standard option as first-line therapy in advanced MGCT patients, whilst they could be an alternative to SDCT regimens in relapsed tumors after proper patient selection.

Recent updates in systemic therapy of breast cancer: A brief narrative review

Breast cancer is the most common malignancy and the leading cause of cancer-related deaths in women globally. Systemic therapy of breast cancer has evolved rapidly in the past few years. In this brief review, we aim to summarize the potentially practice-changing recent updates in the management of breast cancer. We searched the PubMed database for randomized clinical trials for breast cancer treatment conducted over the past 2 years. In addition, abstracts and results of studies reported at major oncology meetings were evaluated. A total of 95 randomized clinical trials were included to prepare this review. Multiple new therapeutic options for almost all subsets of breast cancer have emerged in the past 2 years. Most importantly, for hormone-receptor-positive breast cancer, addition of abemaciclib to endocrine therapy in the adjuvant setting and alpelisib for PIK3CA-mutant refractory advanced disease have been shown to improve the survival outcomes. Addition of pembrolizumab or atezolizumab to neoadjuvant chemotherapy has significantly increased the pathological complete response rate for early triple-negative breast cancer, while adjuvant metronomic capecitabine for 1 year has led to improved disease-free survival. Moreover, adjuvant adotrastuzumab emtansine fared better than trastuzumab in the management of residual disease after neoadjuvant treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer, while tucatinib and neratinib have shown meaningfully improved progression-free survival in HER2-positive advanced disease, including patients with cranial nervous system involvement. Expanding access to these advances is soon expected to transform the way we treat breast cancers.

Management of residual disease after chemotherapy in germ cell tumors.

Although testicular cancer remains a highly curable malignancy, challenges and uncertainty still remain in certain aspects of management. Residual disease after chemotherapy in patients with germ cell tumors (GCT) remains one of these challenges. We aim to highlight the recent literature on the management of residual disease after chemotherapy in GCT and the emerging innovations that may provide further guidance into this area. A subset of patients with GCT will have residual disease after chemotherapy, and management of these patients involves highly skilled multidisciplinary experts including medical oncologists, surgeons, radiologists, and pathologists. Management options depend on histologic subtype, either seminoma or nonseminoma, and involve size criteria, possible further imaging modalities, and tumor markers. Even with these tools at highly specialized expert centers, uncertainty in management remains, and recent literature has explored the use of newer biomarkers to aid in these cases. Postchemotherapy residual masses in GCT can prove to be complicated cases to manage. Balancing survival with quality of life outcomes is important and requires a multidisciplinary team experienced in treating GCT.

Abstract ES11-2: Neoadjuvant Systemic Treatment (NST): Tailoring Response by Sub-type

Abstract Achieving a pathologic complete response (pCR) after neoadjuvant systemic treatment (NST) is clearly associated with improved survival in breast cancer patients, especially with HER2 and triple negative subtypes. In HER2-positive breast cancer patients, the neoadjuvant platform has allowed for the unprecedented accelerated approval for pertuzumab based on improved pCR rates. The KATHERINE trial, in patients who did not achieve pCR following standard trastuzumab/pertuzumab/chemotherapy, demonstrated for the first time that switching to trastuzumab-emtansine (TDM1) led to significant benefit, creating an interesting research paradigm for these high-risk patients with residual disease. For patients with residual disease, the CREATE-X trial demonstrated survival improvement with capecitabine, especially in patients with triple negative disease. New promising agents in the metastatic setting that are being incorporated into NST include immune-check-point inhibitors and cyclin-dependent kinase inhibitors. Evolving technologies like next generation sequencing and gene expression profiles have improved our knowledge regarding the biology of residual disease, and the mechanisms behind treatment resistance, and potentially, metastases. NST allows for testing of new promising treatment regimens - both escalation and de-escalation - depending on sub-types, before surgery. The management and strategies post-NST and the management of residual disease will be discussed. Citation Format: JC Chang. Neoadjuvant Systemic Treatment (NST): Tailoring Response by Sub-type [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES11-2.

LEEP versus cold knife conisation in the management of residual disease after initial LEEP

LEEP versus cold knife conisation in the management of residual disease after initial LEEP

Post-neoadjuvant treatment and the management of residual disease in breast cancer: state of the art and perspectives.

Achieving a pathologic complete response after neoadjuvant treatment is associated with improved prognosis in breast cancer. The CREATE-X trial demonstrated a significant survival improvement with capecitabine in patients with residual invasive disease after neoadjuvant chemotherapy, and the KATHERINE trial showed a significant benefit of trastuzumab-emtansine (TDM1) in human epidermal growth factor receptor 2 (HER2)-positive patients who did not achieve a pathologic complete response after neoadjuvant treatment, creating interesting alternatives of post-neoadjuvant treatments for high-risk patients. New agents are arising as therapeutic options for metastatic breast cancer such as the cyclin-dependent kinase inhibitors and the immune-checkpoint inhibitors, but none has been incorporated into the post-neoadjuvant setting so far. Evolving techniques such as next-generation sequencing and gene expression profiles have improved our knowledge regarding the biology of residual disease, and also on the mechanisms involved in treatment resistance. The present manuscript reviews the current available strategies, the ongoing trials, the potential biomarker-guided approaches and the perspectives for the post-neoadjuvant treatment and the management of residual disease after neoadjuvant treatment in breast cancer.

Primary Systemic Therapy in Breast Cancer: Past Lessons and New Approaches

Primary systemic therapy (PST) is a common treatment strategy used to optimize surgical outcomes for women with locally advanced breast cancer. Several cooperative group trials have shown equivalent survival outcomes between neoadjuvant and adjuvant chemotherapy and have identified pathologic complete response (pCR) as a biologic marker for survival. Research efforts to optimize PST include the development of strategies to predict individual response and to guide the choice of chemotherapy. These emerging approaches are informed by our knowledge of subtypes of breast cancer, as well as genomic technologies, such as chemosensitivity signatures. Following definitive surgery, the management of residual disease is controversial.

Clinical trial update: implications and management of residual disease after neoadjuvant therapy for breast cancer

Clinical trial update: implications and management of residual disease after neoadjuvant therapy for breast cancer

The current role of surgery in the management of residual disease.

The increasing interest in surveillance rather than primary retroperitoneal lymph node dissection for clinical stage I testis cancer has led to retroperitoneal lymph node dissection being performed mostly after chemotherapy for stage II-IV disease. In most centres residual masses of 2-3 cm or more are removed; those smaller than this are most likely to be necrotic. The aim is to remove all residual disease even if this necessitates nephrectomy or excision of adjacent vascular structures. Laparoscopic approaches are hazardous in these circumstances. Thoraco-abdominal surgical approaches enable excellent access to retroperitoneal masses and synchronous excision of ipsilateral pulmonary metastases and thoracic lymph nodes. Retroperitoneal lymph node dissection also appears to be worthwhile in chemotherapy-resistant disease ('desperation retroperitoneal lymph node dissection'), although the relapse rate is higher in this group.

A complicated case of metastatic teratoma: Growing teratoma syndrome and cerebral metastasis

All patients presenting with metastatic teratoma should be regarded as potentially curable and this case demonstrates the multiple treatment modalities which are often needed in the management of such patients. Increasing experience with cisplatin based combination chemotherapy has led to the development of prognostic factors which are used to determine the intensity of treatment given to individual patients. Surgical intervention plays a very important role in the management of residual disease at the completion of chemotherapy. Recognition of the growing teratoma syndrome and the importance of early surgical excision is illustrated by this case. Isolated CNS relapse may occur because the CNS may act as a sanctuary site in patients receiving systemic chemotherapy, but does not preclude long term disease free survival.

Aggressive Surgical Management of Ameloblastoma

SUMMARY, CONCLUSIONS, AND RECOMMENDATIONS The failure of anatomically limited, directly invasive, excisional techniques for the eradication of ameloblastoma has been documented repeatedly in the world's literature for at least 60 years. With the exception of certain unilocular lesions, surgical management in this fashion leads to a need for subsequent operations in at least half of all reported cases so treated.10,37,55 Because of the need for repeated procedures, often of increasing complexity and compromise to the patient's function and appearance, and because of the patient's anxieties evoked by an uncertain prognosis, it is hardly fair to term such surgery “conservative.” To this point, although better understanding and refinement of their applications seems to be developing, neither radiation therapy nor chemotherapy can be considered primary modalities in the treatment of ameloblastoma; their current role remains adjunctive or palliative in the management of residual disease beyond the limits of surgical salvage. Because of their rarity, the reported potentials for metastasis or true malignant degeneration of ameloblastoma cannot be used as realistic foundations to support aggressive, ablative, initial care; rather, the overriding arguments for this approach are its consistently higher rate of success and lessened likelihood of subsequent operations and its toleration by an overwhelming percentage of patients. In these contexts, it would seem unfair to deem such care “radical.” In the clinical sense, the ameloblastoma can be considered a basal-cell carcinoma, to which, in fact, it may well be related histologically. The experienced surgeon will not be intimidated by the prospects this parallel implies, and it falls to him or her to ensure that surgeons of lesser expertise appreciate this parallel in their approaches to this most devastating of odontogenic lesions. Experience suggests several principles in the management of ameloblastoma: 1. Aggressive ablative management, in which the lesion is neither violated nor directly manipulated, is the current treatment of choice and must remain so until consistent long-term evaluation or new knowledge to the contrary is brought to bear. Marginal mandibular resection and other procedures short of discontinuity can fall within this perimeter. 2. Extension of ameloblastoma into the surrounding soft tissues is an ominous sign and demands surgery in those sectors as vigorous as that within the confines of the bone. 3. Current retrospective evaluations of ameloblastoma reappearance rates are essentially meaningless; evaluations must encompass significant numbers of patients for a minimum of 5, and preferably 10, years and, ideally, should be prospective in design. 4. Currently, appropriate periodic evaluation of the patient must include CT and, in certain cases, magnetic resonance imaging. 5. Immediate reconstruction is a legitimate undertaking in the patient operated on in aggressive fashion for elimination of ameloblastoma.

Lymphokine-activated killer (LAK) cells inhibit the clonogenic growth of human leukemic stem cells.

The effect of lymphokine-activated killer (LAK) cells on the in vitro clonogenic capacity of acute myeloid leukemia (AML) blasts was investigated in a semisolid medium assay. The leukemic clonogenic capacity of 11 AML cases, selected on the basis of their ability to grow in vitro, was highly reduced following overnight preincubation with LAK effectors. The degree of colony inhibition, which ranged between 66% and 98% (mean 83.8% +/- 11.4 SD), was quantitatively greater than by 51Cr release, which gave rise to lytic values between 5% and 65% (mean 43.2% +/- 19.2 SD). The demonstration that the clonogenic inhibition was still induced following a shorter pre-incubation period (4 hours) suggests that the effect is unlikely to be due only to the generation of cytotoxic activity during the incubation time. The possibility that LAK cells may be employed in the management of residual disease is strengthened by the evidence that the clonogenic potential of samples containing as few as 20% and 14.3% leukemic cells could be almost completely abolished by LAK effectors. These findings further point the possible role of adoptive immunotherapy with interleukin 2/LAK cells in the treatment of patients with acute leukemia.