Months Of Systemic Chemotherapy Research Articles

PIPAC in patients with peritoneal metastases from gastrointestinal tract (PIPOX): An open label, non-comparative phase 1/2 dose escalation and expansion trial.

e15561 Background: Withmodern systemic chemotherapy, survival remain poor for patient withadvanced isolated peritoneal metastases from gastrointestinal tract. We aimed to assess the safety and efficacy of PIPAC to oxaliplatin in combination or not with systemic chemotherapy. Methods: We did a phase 1/2, open label, non-comparative, dose escalation and expansion trial of PIPAC to oxaliplatin forpatients with peritoneal cancer index (PCI) more than 5, 13 and 15 for respectively a gastric, small bowell and colorectal cancer primary; who had received at least three months of systemic chemotherapy. PIPAC cycle lengths was 4 to 6 weeks with systemic chemotherapy allowed 15 days after each PIPAC. PCI and oxaliplatin concentration tumor was assessed every PIPAC cycles. Main endpoints were, tolerability, tumor response and survival. Results: Between2017 to 2020, 34 for patients were enrolled in three centers, in this phase 1/2 study of whom 25 were evaluable at recommanded dose of phase I of 90 mg/m2 plus systemic 5-FU. At this dose, safety profile showed acceptable tolerability. 8 patients (32%) had grade 3/4 treatment related adverse event. Minors (grade 1/2) adverse events were mainly abdominal pain (n = 19, 76%) and nausea (n = 16, 64%). Before inclusion patients received a median of 2 [1-4] chemotherapy lines and had a median PCI of 22.5 [7-29]. Median PFS was 6.1 months and median OS was 13 months. Conclusions: In patients with advanced and refractory peritoneal metastasis, PFS of 6.1 months is encouraging. A prospective randomized phase II study is required. Clinical trial information: NCT03294252 .

Outcomes of patients with peritoneal carcinomatosis treated with HIPEC and chemotherapy or HIPEC alone: A single center community experience.

e15578 Background: Peritoneal carcinomatosis is a common presentation of intraperitoneal malignancies. The optimal management of peritoneal carcinomatosis is currently unknown but can contain a combination of HIPEC and chemotherapy. Optimal timing and order of these interventions is controversial. HIPEC surgery alone can provide a cure rate of approximately 16% with macroscopically complete resection. The PRODIGE 7 trial demonstrated no difference in overall survival between HIPEC plus cytoreduction versus cytoreduction alone with six months of systemic chemotherapy. Which patients should receive HIPEC, chemotherapy and HIPEC or chemotherapy alone remains unknown. Methods: This is a single center, retrospective chart review assessing all patients age 18 and above who received HIPEC surgery with and without the administration of chemotherapy at Ascension Saint John Hospital. Results: We found that there was no significant difference in overall survival and progression free survival between the HIPEC and HIPEC with chemotherapy group with a OS of 57.2 months and 52.5 months; and PFS of 33.6 and 34.4 months respectively. We found that patients with a PCI score between 0 and 13, overall survival favored the HIPEC alone group versus the HIPEC with chemotherapy with a p value of 0.043. There was no difference in progression free survival and overall survival in all other groups when stratified by PCI. When stratified by disease subtype, we no differences between PFS and OS for both appendiceal and colon cancer. Conclusions: The primary objective of this study was to investigate the difference in overall survival and progression free survival among patients with peritoneal carcinomatosis when treated with either HIPEC with systemic chemotherapy versus HIPEC alone. This analysis among 100 patients showed no statistically significant differences in OS or PFS for patients receiving a combination of HIPEC with systemic chemotherapy versus HIPEC alone. The only exception to this was with respect to OS in patients with a PCI score between 0-13. In this group, 0 patients in the HIPEC along group experienced disease progression where 5 progressed in the HIPEC and chemotherapy group. Our data suggests that HIPEC alone may be a reasonable treatment approach for patients with a low PCI score. Important conclusions can be drawn from the data when compared to historical trials. The PROTEGE 7 study found that the median overall survival was approximately 41.7 months for the HIPEC and cytoreductive surgery group and 41.2 months versus cytoreductive surgery alone. The overall survival for the HIPEC alone group was 57.2 months and 52.5 months for the HIPEC plus chemotherapy group. This data suggests that the combination of HIPEC and chemotherapy is a reasonable approach to patients with peritoneal carcinomatosis.

Oncologic Outcomes of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Highly Selected Patients with Metastatic Pancreatic Ductal Adenocarcinoma.

Peritoneal metastases (PM) from pancreatic ductal adenocarcinoma (PDAC) are currently treated with palliative systemic chemotherapy alone, with unsatisfactory results. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may provide an oncologic benefit for highly selected patients. Patients with PDAC and isolated PM who completed ≥ 6 months of systemic chemotherapy with objective response between 2017 and 2022 were retrospectively reviewed. All patients met the inclusion/exclusion criteria as per our previously published PDAC CRS/HIPEC protocol. Patients who underwent CRS/HIPEC were compared with matched patients who underwent systemic therapy alone. Overall survival (OS) from diagnosis of PM and progression-free survival (PFS) from CRS/HIPEC was evaluated. In total, 61 patients met the inclusion criteria: 38 underwent systemic therapy alone and 23 CRS/HIPEC. There were no differences in baseline prognostic factors, including age, sex, tumor size, tumor location, anatomic resectability, or serum cancer antigen (CA) 19-9 (p > 0.05). Median OS from PM diagnosis in patients who underwent systemic therapy alone was 19 months with 1, 2, and 3 year OS of 81%, 31%, and 8%, respectively. In contrast, median OS from PM diagnosis in patients who underwent CRS/HIPEC was 41 months with improved 1, 2, and 3 year OS of 91%, 66%, and 59%, respectively (p = 0.002). In the 21 patients who achieved complete cytoreduction (CC-0), no adjuvant therapy was administered and the median PFS was 17 months. CRS/HIPEC in highly selected patients with PDAC and PM results in promising oncologic outcomes that are unlikely to be achieved with systemic chemotherapy alone. Further investigation is warranted and ongoing (NCT04858009).

Cytoreduction with Hyperthermic Intraperitoneal Chemoperfusion for Pancreatic Cancer with Low-Volume Peritoneal Metastasis: Results from a Prospective Pilot Study.

Resection of oligometastatic pancreatic ductal adenocarcinoma (PDAC) has historically been ineffective, however modern systemic chemotherapy has improved survival. Thus, re-evaluating safety and outcomes of surgical resection in selected patients with limited peritoneal metastasis (PM) warrants consideration. From 2018 to 2021, patients with PDAC and positive cytology or limited PM without extraperitoneal metastasis and who had an objective response to ≥ 6 months of systemic chemotherapy were enrolled. Patients underwent laparoscopic hyperthermic intraperitoneal chemotherapy (HIPEC) with cisplatin/mitomycin C. If amenable to a complete cytoreduction, patients went on to cytoreduction and HIPEC. Overall, 18 patients were enrolled and received a median of 14 (interquartile range [IQR] 12-17) cycles of chemotherapy; 16 (89%) patients received chemoradiation. Laparoscopic HIPEC was completed in 17 patients, with a median length of stay of 1day, and no grade III complications or hematological toxicities were observed. All 18 patients subsequently underwent a complete cytoreduction (CC-0) along with definitive treatment of the primary tumor, with formal resection (7/18), irreversible electroporation (IRE; 10/18), or intraoperative radiation therapy (IORT; 1/18). Median PCI was 2 (IQR 0-4), median LOS was 7 days (IQR 6-8), and 7 (39%) patients were readmitted. Eight (44%) patients experienced grade 3 or higher complications, including one 30-day mortality. At a median follow-up of 16 months, the median progression-free survival was 20 months and the median overall survival was 26 months. Cytoreduction and HIPEC for selected patients with low-volume PMfrom PDAC is safe and feasible with favorable short-term outcomes. A phase II trial (NCT04858009) is now enrolling to further assess this multimodality approach in select patients.

ORAL HIV-ASSOCIATED KAPOSI'S SARCOMA WITH ATYPICAL CLINICAL PRESENTATION: REPORT OF A CASE

Kaposi's sarcoma is a multifocal angioproliferative malignant neoplasm caused by human herpesvirus 8 (HHV-8) and commonly associated with acquired immunodeficiency syndrome (AIDS). A 25-year-old male patient recently diagnosed with AIDS was referred for consultation reporting multiple intraoral lesions with 2 months of evolution. Physical examination revealed diffuse multinodular purplish-red lesions of fibroelastic consistency, associated with spontaneous bleeding, affecting the whole maxillary and mandibular keratinized mucosa. Incisional biopsy was performed. Histopathologic examination revealed a mucosal fragment covered by stratified squamous epithelium exhibiting a large amount of blood vessels in the connective tissue and vascular proliferation associated with a large number of spindle-shaped neoplastic cells and red blood cell extravasation. Immunohistochemistry for HHV-8 was positive, confirming the diagnosis of Kaposi's sarcoma. After 3 months of systemic chemotherapy with liposomal doxorubicin the patient showed improvement of the oral lesions.

Survival in total preoperative verus perioperative chemotherapy for patients with metastatic high-grade appendiceal adenocarcinoma undergoing CRS/HIPEC.

90 Background: Due to the relative infrequency of high grade appendiceal adenocarcinoma with peritoneal metastases, there is limited data to guide treatment strategies. Current practices for this disease are largely extrapolated from colon cancer patients with peritoneal metastases, who typically undergo six months of systemic chemotherapy in conjunction with cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). The optimal timing of chemotherapy in relation to CRS/HIPEC remains unknown. In this study, we compare the efficacy of peri-operative chemotherapy to pre-operative chemotherapy alone. Methods: This is a retrospective review of patients who underwent CRS/HIPEC for high grade appendiceal cancers from a tertiary referral center from 2014-2020. Outcomes were compared between patients who underwent planned 6 months of chemotherapy followed by CRS/HIPEC (pre-operative group) versus planned 3 months of chemotherapy both pre- and post-operatively (peri-operative group). Results: 85 patients were treated for metastatic high-grade appendiceal cancers during the study period, of whom24 were eligible for inclusion. Of those included, 16 were in the peri-operative group and 8 in the pre-operative group. Most patients were white (75%), non-Hispanic (96%) and female (54%). Patients in the pre-operative group tended to be older (65 vs. 56 years, p = 0.02). For patients with specified histologic grading, poorly differentiated tumors were common (50%). Signet ring cell histology (42%) and mucinous features (67%) were frequent as well. Median overall survival was similar between the pre-operative and peri-operative groups (32.3 vs. 31.6 months, p = 0.97), although patients undergoing peri-operative treatment received fewer total cycles of chemotherapy on average (14.1 vs. 9.5 cycles, p < 0.01). Half of the patients in the peri-operative group (8/16) did not complete their chemotherapy regimen, with 75% discontinuing therapy due to chemotherapy-related toxicities. Within the peri-operative group, a non-significant decrease in median survival was observed for those who did not complete chemotherapy (27.8 vs > 53.6 months, p = 0.22). Conclusions: Peri-operative and total pre-operative chemotherapy strategies are associated with similar survival in patients with high grade appendiceal cancers undergoing CRS/HIPEC. Peri-operative administration may be limited by chemotherapy-related toxicities.

SEOM clinical guidelines for pancreatic and biliary tract cancer (2020)

Pancreatic cancer (PC) and biliary tract cancer (BTC) are both aggressive and highly fatal malignancies. Nowadays we have a profound knowledge about the molecular landscape of these neoplasms and this has allowed new therapeutic options. Surgery is the only potentially curative therapy in both cancers, but disease recurrence is frequent. In PC, adjuvant treatment with mFOLFIRINOX has improved overall survival (OS) and in BTC adjuvant treatment with capecitabine seems to improve OS and relapse-free survival. Concomitant radio-chemotherapy could also be considered following R1 surgery in both neoplasms. Neoadjuvant treatment represents the best option for achieving an R0 resection in borderline PC. Upfront systemic chemotherapy is the treatment of choice in unresectable locally advanced PC and BTC; then locoregional therapy could be considered after an initial period of at least 3–4 months of systemic chemotherapy. In metastatic PC, FOLFIRINOX or Gemcitabine plus nab-paclitaxel have improved OS compared with gemcitabine alone. In metastatic BTC, cisplatin plus gemcitabine constitute the standard treatment. Progress in the knowledge of molecular biology has enabled the identification of new targets for therapy with encouraging results that could in the future improve the survival and quality of life of patients with PC and BTC.

Results of the randomized phase II portion of NRG Oncology/RTOG 0848 evaluating the addition of erlotinib to adjuvant gemcitabine for patients with resected pancreatic head adenocarcinoma.

4007 Background: NRG/RTOG 0848 is a 2-step study designed to determine whether erlotinib (E) added to gemcitabine (G) (randomized Ph II) &/or adjuvant radiation with concurrent 5-FU or capecitabine following 6 months of systemic chemotherapy (Ph III), improve survival in patients (pts) with resected pancreatic head adenocarcinoma. The erlotinib results are reported here. Methods: Eligible pts include those with resected pancreatic head adenocarcinoma, pathologic stage T1-T3, N0-1, M0; PS 0-1, & CA19-9 ≤ 180 IU/L. Pts in Arms 1 & 2 received G 1 gm/m2 weekly for 3 weeks in a 28-day cycle for 6 cycles. Pts in Arm 2 also received E 100 mg/day. The primary hypothesis for the E portion was that G+E would increase overall survival (OS) compared to G alone. With a 1-sided alpha of 0.15, 200 OS events provide 80%/90% power to detect a signal for an increase in median OS from 22 to 28.8/30.6 months (mos). OS was estimated by the Kaplan-Meier method & arms compared using the log rank test. The Cox proportional hazards model was used to analyze treatment effect. Results: 336 pts were randomized from 11/17/2009 to 2/28/2014, with 163 pts evaluable for G and 159 for G+E. Median age was 63 years (39-86). Most pts had pathologic T3 disease (78%) & CA19-9 ≤ 90 (93%). There are 32 pts (20%) with grade 4 adverse events (AEs) & 2 pts (1%) with grade 5 AEs on G and 27 (17%) & 3 (2%) on G+E arm, respectively. There are fewer grade ≥ 3 GI AEs on the G arm (22%) as compared to the G+E arm (28%), and 110 (69.2%) & 93 (59.6%) pts received at least 85% of planned G dose for the G & G+E arms, respectively. 58% of E pts received at least 85% of planned E dose. The median follow-up for alive pts is 42.5 mos (min-max: < 1-75). With 203 deaths, median & 3-yr OS (95% CI) are 29.9 mos (21.7-33.4) & 39% (30, 45) for G and 28.1 mos (20.7-30.9) & 39% (31, 47) for G+E; log-rank p = 0.62. The hazard ratio (95% CI) comparing OS of G+E to G is 1.04 (0.79- 1.38). Conclusions: The addition of adjuvant E to G did not provide a signal for increased OS in pts with resected pancreatic head cancer compared to G alone. Accrual to the trial is continuing to answer the Ph III radiation question. Clinical trial information: NCT01013649.

Prolonged Neoadjuvant Therapy for Locally Advanced Pancreatic Cancer

Purpose: The purpose of this study was to investigate if prolonged neoadjuvant therapy, for locally advanced pancreatic cancer could be used to identify those patients who could benefit from resection surgery. Methods: Thirty-four patients with locally advanced pancreatic cancer invading the adjacent major arteries underwent chemoradiotherapy, followed by 6 months of systemic chemotherapy, unless their tumor was already resectable. After this combination treatment, surgical resection was performed on those patients with tumors judged to be at least borderline resectable. Results: Reevaluation after chemoradiotherapy revealed that, at that stage, surgery was only possible for one case; resection was successfully performed. Following 6 months of systemic chemotherapy, a further 7 patients were diagnosed with borderline resectable lesions; 4 underwent surgery with no postoperative complications. The median survival time of the patients following surgery was 3.63 years; this was reduced to approximately a third in patients not undergoing surgery (1.01 years; p = 0.0005). Conclusions: For patients with locally advanced pancreatic cancer, prolonged neoadjuvant therapy was successfully used to select candidates that could benefit from surgical resection of their tumor. Resection significantly increased the long-term survival rate.

Quality of Care Review: Some Progress, and Toward What Goal?

TO THE EDITOR: Drs Lorenz and Ganz brought together a stellar group of investigators providing a comprehensive review on quality of care and supportive care in oncology. I commend the authors for stating up front that an examination of quality of care in oncology needs to include not only the supportive and end-of-life aspects, but also the entire spectrum of clinical care. However, having emphasized the multidisciplinary aspects of palliative care, the authors failed to review the progress of supportive care in surgical and radiologic treatments of the cancer patient. One of the most important contributions of health-related quality-of-life research to clinical care is the inclusion of patient and family input into the decision-making process for the treatment of cancer. Whether the decision is to proceed with a major curative operation or embark on several months of systemic chemotherapy, the decision-making process has largely been based on survival and morbidity-mortality rates, performance status, molecular markers, and other clinical end points. The patient may be provided with a detailed explanation of the scientific basis of the treatment options. However, patient and family involvement in the decision-making process has been peripheral. Today, the patient can choose among several treatment options resulting in better quality of life, and sometimes not take advantage of the curative potential of other, more disabling treatment options. For example, neoadjuvant chemotherapy with complete or partial responses can allow organ preservation with minimal compromise in eventual survival rates. The need for additional research in quality of care has been outlined by several authors. In oncologic surgical care, the need for research into quality of care and palliative surgery has been underestimated. Just as quality-of-life measures have been incorporated into several phase III trials, these measures should also be incorporated into newer, minimally invasive surgical treatment evaluations. Lack of awareness and underuse of supportive care services have also been well documented. There is a general consensus about the need to evaluate quality of care. However, there is neither a consensus nor a clinical standard in the measure of quality of care. These measures need to be simple and easily applied at the bedside or clinic. The adopted measure has to be reproducible among different investigators and clinicians across different institutions. The end points from these measures need to be consistent with other clinical standards, and when applied to patient care, the results will indicate improved, cost-effective patient management.

Usefulness of FDG PET for diagnosis and radiotherapy of the patient with malignant lymphoma involving bone marrow

We experienced a case of relapsed malignant lymphoma with multiple bone marrow or bone lesions. The case was diagnosed as follicular lymphoma by cytological biopsy of the right iliac bone, with (67)Ga scintigraphy showing abnormal, intense uptake in multiple bones. After about 10 months of systemic chemotherapy, a relapse was suspected because of pain in the bilateral legs and a high level of lactate dehydrogenase. Assessment of the lesions in the patient was difficult by computed tomography because the affected sites were localized mainly in the bone marrow. (18)F-Fluorodeoxyglucose (FDG) positron emission tomography (PET) was useful for detecting accurately the relapse sites in the bone marrow and enabled us to determine the field for radiotherapy. There are only a few reports of FDG-PET findings for such bone marrow malignant lymphomas. Therefore, we report the findings of FDG-PET for this case and review some of the literature about bone marrow lymphomas.

Cutaneous metastasis resembling acute dermatitis in patient with advanced gastric cancer

The most common metastatic sites from gastric cancer are the liver, intra-abdominal lymph nodes, ovary and peritoneal cavity. Cutaneous metastasis of gastric cancer is rare, and most cutaneous metastases are typically solitary, nodular, have a firm consistency, and are red or hyperpigmented. Thus, cutaneous metastasis is easily distinguished from other skin disease. We report a case of a 60-year-old woman with cutaneous metastasis of gastric cancer, whose facial skin showed painless pruritic eczema, resembling acute dermatitis. She had earlier undergone a total gastrectomy for advanced gastric cancer in our hospital. After 14 months, she developed eczematous facial lesions; the presumptive diagnosis was acute dermatitis. However, skin biopsy unexpectedly revealed cutaneous metastasis of gastric cancer. After 6 months of systemic chemotherapy with capecitabine and cisplatin, the cutaneous metastasis was markedly improved and a clinically complete remission was accomplished.

Definitive surgery and multiagent systemic therapy for patients with localized Ewing sarcoma family of tumors

The local management of Ewing sarcoma family of tumors (ESFT) often centers on the surgical resectability of the primary lesion and physician biases regarding differences in the morbidity between primary surgical and radiotherapeutic management. The authors retrospectively reviewed the records of 33 patients with localized ESFT who underwent surgery and received systemic chemotherapy at St. Jude Children's Research Hospital (Memphis, TN). Two multiagent systemic chemotherapy regimens were used: 14 patients received vincristine, doxorubicin, cyclophosphamide, and actinomycin D (VACA), and 19 received VACA in combination with ifosphamide and etoposide. The primary tumor was surgically resected via a wide, local excision (n = 32) or a marginal excision (n = 1)performed either at diagnosis or after 3-5 months of systemic chemotherapy. Clinical outcome and prognostic factors for disease control were reported in the current study. The median follow-up for patients was 9.9 years. The 5-year and 10-year survival rates were 84.5% and 75.8%, respectively. At 5 years, the cumulative incidence of local disease recurrence was 12.5%, and the event-free survival (EFS) rate was 71.7%. The same values were found at 10 years. The site of tumor origin was a significant predictor of EFS. The survival rate of patients whose tumors arose in bone was 78.6%, and the survival rate of patients whose tumors originated in soft tissue was 25.0% (P = 0.028). No other factors investigated were predictive of outcome. Local disease control and overall outcome for patients with ESFT managed by multiagent systemic therapy and surgery was excellent. Local disease control rates remained near 90% at 10-year follow-up. Patients with extraosseous primary sites of disease may fare less well with this approach to therapy.

Hepatic resection following systemic chemotherapy for metastatic colorectal carcinoma.

Increasingly effective systemic chemotherapy has improved responses in patients with previously unresectable colorectal hepatic metastases. In the future, response to chemotherapy may define a new population of patients that may benefit from hepatic resection. A retrospective review to determine the safety and effectiveness of potentially curative hepatic resection of metastatic colorectal carcinoma after systemic chemotherapy identified 11 such patients with resections between July 1987 and October 1991. Five patients had unresectable disease confined to the liver, two had hepatic and limited extrahepatic metastases, two had hepatic recurrences after previous hepatic metastasectomy, and two had initially resectable liver metastases. These patients were resected after a mean of 8 months of systemic chemotherapy. Complications, usually minor, occurred in five patients (45%). There were no deaths. Three patients are disease free at 15, 18, and 31 months (mean 21) after hepatic resection. Eight patients have recurred with a median time to recurrence of 8 months. Five patients have subsequently died of recurrent disease. This study suggests that hepatic resection following systemic chemotherapy can be performed safely and may benefit selected patients.

Definitive irradiation for localized non-Hodgkin's lymphoma of breast

A diagnosis of primary non-Hodgkin's lymphoma (NHL) confined to the breast or breast and ipsilateral lymph nodes was biopsy proven in 19 patients who presented to our institution between 1970 and 1984. Four patients were treated with a modified radical mastectomy, and one with chemotherapy only. The remaining 14 patients comprise the basis of this study. All patients were clinically staged. There were 12 patients with 1A-E disease and two with IIA-E disease. All patients were treated with breast radiation. The axillary nodes were included in seven of the patients and two, in addition, received “mantle” irradiation. The majority of the patients received between 3500–4400 cGy, but four received lower doses. One patient, with Stage IIA-E disease, received 6 months of systemic chemotherapy, followed by 3500 cGy to the breast and axilla. Three of the 14 patients relapsed within the treated area, with a local control rate of 78%. One was salvaged with a mastectomy and remains alive and well 15 years after diagnosis. Seven of the 14 patients relapsed distantly, including two with local failures, but only three have died of disease. An additional two patients have died of other causes without evidence of disease, for a survival of 66% at 48 months (Kaplan-Meier Calculations).

Cardiac Tamponade as First Manifestation of Colonic Cancer

Metastatic cardiac tamponade was the presenting manifestation of a colonic carcinoma. The patient's condition improved after surgical treatment and shows no sign of recurrence of pericardial effusion after more than eight months of systemic chemotherapy. Metastatic pericardial effusions and their treatment are discussed.