Re-irradiation and hyperthermia after surgery for recurrent breast cancer

Purpose

Evaluation of efficacy and side effects of combined re-irradiation and hyperthermia electively or for subclinical disease in the management of locoregional recurrent breast cancer.

Methods and materials

Records of 198 patients with recurrent breast cancer treated with re-irradiation and hyperthermia from 1993 to 2010 were reviewed. Prior treatments included surgery (100%), radiotherapy (100%), chemotherapy (42%), and hormonal therapy (57%). Ninety-one patients were treated for microscopic residual disease following resection or systemic therapy and 107 patients were treated electively for areas at high risk for local recurrences. All patients were re-irradiated to 28–36 Gy (median 32) and treated with 3–8 hyperthermia treatments (mean 4.36). Forty percent of the patients received concurrent hormonal therapy. Patient and tumor characteristics predictive for actuarial local control (LC) and toxicity were studied in univariate and multivariate analysis.

Results

The median follow-up was 42 months. Three and 5 year LC-rates were 83% and 78%. Mean of T90 (tenth percentile of temperature distribution), maximum and average temperatures were 39.8 °C, 43.6 °C, and 41.2 °C, respectively. Mean of the cumulative equivalent minutes (CEM43) at T90 was 4.58 min. Number of previous chemotherapy and surgical procedures were most predictive for LC. Cumulative incidence of grade 3 and 4 late toxicity at 5 years was 11.9%. The number of thermometry sensors and depth of treatment volume were associated with acute hyperthermia toxicity.

Conclusions

The combination of re-irradiation and hyperthermia results in a high LC-rate with acceptable toxicity.     

Re-irradiation for locally recurrent refractory breast cancer

Purpose

To report an analysis of treatment outcomes of a cohort of patients re-irradiated for locally recurrent refractory breast cancer (LRRBC)

Patients and Methods

Between 2008 and 2013, 47 women (mean age = 60 years) were re-irradiated for LRRBC. Outcomes were measured using Kaplan-Meier log rank to compare curves and Cox regression for multivariate analysis. Outcomes included overall survival (OS), time to re-treatment, survival without systemic progression, and survival without local recurrence.

Results

Fifty-six instances of re-irradiation were completed and analyzed. The mean cumulative 2 Gy equivalent dose (EQD2) to the whole breast and tumour cavity (α/β = 3) was 99.8 Gy and 109.1 Gy, respectively. Most patients initially had significant symptoms before RT due to local recurrence. The median time to re-treatment and to systemic failure was 41 and 50 months, respectively. Median follow-up for OS was 17 months and OS was 0.73 (SE = 0.07) at 1 year and 0.67 (SE = 0.07) at 2 years. Local control was 0.62 (SE = 0.07) and 0.5 (0.08) at 1 and 2 years, respectively. Acute radiation dermatitis was G1-2, G3 and G4 in 45, 4 and 1 cases, respectively. One patient presented with necrosis. The most common long term toxicity was G3 fibrosis (n = 4) and telangiectatic changes (n = 3). Multivariable analysis indicated that skin involvement (Hazard Ratio = 6.6 (1.4-31), p = 0.016) and time to local recurrence <2yr (HR 3.1 (1.04-9.7) p = 0.042) predicted local recurrence.

Conclusion

High dose re-irradiation is feasible for locally RRBC. This approach can have a significant benefit in this very high-risk group.     

Forequarter amputation for recurrent breast cancer: a case report and review of the literature

Axillary recurrence of breast cancer is an uncommon event that can lead to debilitating pain, lymphedema, and paralysis of the upper extremity. Multimodality therapy including surgery is usually used to control local recurrence. In a subset of patients, the extent of disease is such that local excision of the recurrence is not possible. In the absence of metastatic disease, forequarter amputation may be used as an effective means of surgical salvage and palliation for locally recurrent breast cancer. In this report, we describe management of a patient with advanced axillary recurrence treated with forequarter amputation and review the current literature on the use of this operation in breast cancer patients.     

Obesity obscuring breast cancer: a case report.

There is normally a layer of fat in the breast between the parenchyma of the breast and the skin. This is frequently thin and does not preclude the palpation of a tumor mass which involves the breast parenchyma. In patients suffering from obesity this fat pad becomes much thicker and obscures any underlying masses arising from the breast parenchyma. A case is reported in which a woman who was markedly obese lost a significant amount of weight and presented a bulge which was found to be carcinoma. This situation, in which fat obscures underlying breast lesion, has been observed in a number of patients. Attention is called to the limited value of physical examination of the breast in markedly obese patients. If any suspicion exists or if the patient is a candidate for cancer from a familial standpoint, mammograms are indicated.     

Locally recurrent endometrial cancer: a case report

Endometrial cancer is the most common malignancy of the female genital tract. It is typically a disease of postmenopausal women and often presents with postmenopausal vaginal bleeding. In 75% of cases, it is diagnosed at an early stage and is associated with better overall survival rates than many malignancies. The appropriate staging surgery for patients diagnosed with endometrial cancer is a total hysterectomy and bilateral salpingo-oophorectomy with pelvic and para-aortic lymphadenectomy. Adjuvant radiation therapy in early-stage disease is associated with decreased rates of locoregional recurrences but does not improve overall survival. The role of chemotherapy is not well established for early-stage disease. Treatment recommendations for locoregional recurrence of endometrial cancer after hysterectomy are poorly defined and include tumor-directed radiation therapy, and/or chemotherapy, and/or surgical resection. Because the current guidelines are not specific, they are confusing to clinicians. To illustrate this, this report presents a patient who was diagnosed with stage IA endometrial cancer and developed vaginal cuff recurrence 3 months after surgery.     

Thermoradiotherapy for residual microscopic cancer: elective or post-excisional hyperthermia and radiation therapy in the management of local-regional recurrent breast cancer.

A Phase I/II study was undertaken to investigate the efficacy and side effects of combined hyperthermia and radiation therapy in the management of presumed or known microscopic residual tumors. Between February 1985 and March 1991, 262 fields in 89 patients with local-regional recurrent breast cancer were treated with externally administered hyperthermia and radiation therapy. Thirty-eight fields were treated for microscopic residual disease following excisional biopsy of nodular recurrences and 224 fields were treated electively for areas at high risk for local recurrences adjacent to fields with macroscopic residual disease. Mechanically mapped temperatures were monitored throughout the field in all treatments. All patients had at least one follow-up evaluation at three weeks or more following completion of treatment. The majority of the fields were in patients who had had extensive prior therapy including radiation therapy (54%), chemotherapy (71%), and hormonal therapy (51%). All fields received hyperthermia (1-6 treatments: average 1.74) and radiation therapy (average dose: 42.4 Gy); concurrent hormonal therapy was administered in 37% of the treatments and no fields received concurrent chemotherapy. The treatments were well tolerated, no life-threatening complications were noted. Averages for all fields of the minimum, maximum, and average measured interstitial temperatures were 40.2 degrees C, 45.3 degrees C, and 42.8 degrees C, respectively. The three-year actuarial local-control rate for all 262 treated fields was 68%. Parameters characterizing the initial breast cancer, the patient and tumor at the time of hyperthermia, and the treatment were studied in univariate and multivariate analysis for correlation with duration of local control within the hyperthermia treatment field. Parameters in the best five covariate model correlating with the duration of local control included: estrogen receptor status of the initial breast cancer; initial T-stage; time from initial breast cancer to first failure; age at hyperthermia; and concurrent radiation dose (p-value for model less than 0.000001). Six covariate models adding anatomic site of disease, field type, mean minimum temperatures, and mean percent temperatures greater than or equal to 40 degrees C all resulted in improved models. Randomized controlled studies stratifying for these pretreatment parameters are felt warranted to confirm the value of adjuvant hyperthermia in the elective treatment of areas of high risk for local-regional recurrent breast cancer and in fields following surgical excision of recurrent disease, particularly in patients in whom full dose radiation therapy cannot be safely administered.     

Multifocal male breast cancer: a case report

Breast cancer among men is rare and accounts for < 1% of all breast cancer diagnoses. We report a 75-year-old man who presented with a painless breast lump and was found to have 2 separate foci of cancer in the same breast. Several cases of bilateral male breast cancer exist in the literature, but we are not aware of any previous reports of multifocal male breast cancer. Key issues surrounding the diagnosis and treatment of multifocal male breast cancer are discussed.     

Re-irradiation for recurrent rhabdomyosarcoma of the nasopharynx in a child

There are few clinical situations where high dose re-irradiation with curative intent is indicated in children. Because of the potential for serious late sequelae, re-irradiation is considered only in the unusual situation where there is just local recurrence and surgery and/or chemotherapy are unlikely to provide long-term control. The authors present a case of nasopharynx rhabdomyosarcoma in a child which recurred after high dose irradiation and chemotherapy and was then re-irradiated to a high dose. The child is well without any serious sequelae more than 13 years following completion of the second course of radiotherapy.     

Primary orbital liposarcoma in Li-Fraumeni cancer family syndrome: a case report

AIMS AND BACKGROUND: The aim of this study was to describe a case of primary orbital liposarcoma in Li-Fraumeni syndrome. METHODS AND STUDY DESIGN: In July 1998 a 20-year-old woman with a histological diagnosis of orbital myxoid liposarcoma underwent surgical treatment in our department. Since the patient's family pedigree met the clinical criteria for the diagnosis of LFS, molecular analysis was performed, which resulted in a molecular profile consistent with Li-Fraumeni syndrome. RESULTS: The patient underwent orbital exenteration extended to the upper eyelid; surgical reconstructive steps were performed to permit placement of an orbital prosthesis. Two years after primary surgery the patient underwent a quadrantectomy with lymphadenectomy of the right axilla because of the presence of a nodule of 1.5 cm in diameter in the upper-lateral quadrant of the right breast. One year after the last surgery, the patient is disease free. CONCLUSION: The diagnosis of an orbital malignancy in a young patient with a family history of cancer should suggest the presence of an underlying genetic disorder like LFS; with molecular analysis we can now determine the genetic disorder and the exact location of the mutation, and also obtain important prognostic data using specific cellular markers. More prognostic information increases the chances of adequate personalized treatment.     

Bilateral male breast cancer and prostate cancer: a case report

Male breast cancer, consisting only 1% of all breast cancers, is occasionally associated with other primary malignancies, especially in patients with familial breast cancer history. Sporadic male breast cancers with another primary tumor are extremely rare. We report a 67-year-old male with asynchronous bilateral breast cancer and prostate cancer without familial breast cancer history.     

Reirradiation combined with hyperthermia in recurrent breast cancer results in a worthwhile local palliation

Both experimental and clinical research have shown that hyperthermia (HT) gives valuable additional effects when applied in combination with radiotherapy (RT). The purpose of this study was evaluation of results in patients with recurrent breast cancer, treated at the Daniel den Hoed Cancer Center (DHCC) with reirradiation (re-RT; eight fractions of 4 Gy twice weekly) combined with HT. All 134 patients for whom such treatment was planned were included in the analysis. The complete response rate in 119 patients with macroscopic tumour was 71%. Including the 15 patients with microscopic disease, the local control rate was 73%. The median duration of local control was 32 months, and toxicity was acceptable. The complete response (CR) rate was higher, and the toxicity was less with the later developed 433-MHz HT technique compared with the 2450-MHz technique used initially. With this relatively well-tolerated treatment, palliation by local tumour control of a worthwhile duration is achieved in the majority of patients. The technique used for hyperthermia appeared to influence the achieved results. The value of HT in addition to this re-RT schedule has been confirmed by a prospective randomized trial in a similar patient group. In The Netherlands, this combined treatment is offered as standard to patients with breast cancer recurring in previously irradiated areas.     

Accessory breast cancer: A case report of carcinoma originating from aberrant breast tissue in the axillar region

A 74 year-old woman with accessory breast cancer in the left axillar region had a painful mass in the left axillar region. Physical examination revealed a mass of about 3 cm in diameter with hemorrhagic ulceration of the skin. The movements of her left arm were severely limited because of the pain. A biopsy specimen showed malignant metastatic tissues, whereas the gallium scintigram and bone scintigram disclosed multiple systemic metastases. Though radical cure could not be achieved surgically, she underwent local resection of the left axillar mass to alleviate the clinical symptoms. The histopathological examinaton revealed a solid tubular adenocarcinoma combined with scirrhous type adnocarcinoma, which was compatible with that of breast cancer. Her clinical symptoms were remarkably improved after operation and then she was followed up at the outpatient clinic. However, she died of respiratory failure due to pleural metastases 10 months after operation.     

Re-irradiation in conjunction with liposomal doxorubicin for the treatment of skin metastases of recurrent breast cancer: a radiobiological approach and 2 year of follow-up

Thirty patients with local relapses after radical mastectomy and radiotherapy and undergoing infusion of liposomal doxorubicin (40 mg/m(2) monthly for 6 months) were randomized to receive re-irradiation. Radiotherapy was with either 17 fractions of 1.8 Gy, 5 days a week (N=15, group A) or 4 Gy plus two fractions of 3 Gy the 1st week and six fractions of 3 Gy given every second day (N=15, group B). Eight patients from group A (53.3%) and nine patients (60%) from group B demonstrating a clinically complete response (P=0.9). Grade I/II acute skin toxicity was monitored in 26.6% of patients in group A versus 73.3% in group B. The radiation schedule of group A seems superior for grade I/II acute (P=0.027) and late (P=0.015) skin toxicity. The linear quadratic model enabled the prediction of tumor response as well as normal skin reactions.     

Pegylated liposomal doxorubicin in combination with hyperthermia for treatment of skin metastases of breast carcinoma: a case report.

BACKGROUND: Incorporation of doxorubicin hydrochloride into pegylated liposomes (PLD) may decrease chemotherapy side effects and increase the activity. Hyperthermia could further potentiate its effectiveness. CASE REPORT: A patient with skin metastases of breast carcinoma was treated with intravenous infusion of PLD (Caelyx) in combination with ultrasound hyperthermia. Each cycle consisted of infusion of 40 mg PLD absolute dose, followed by 2 fractions of hyperthermia 41-43 degrees C for 45 min 1 and 48 h after infusion. A complete remission was observed after the combination treatment with no significant toxicity. CONCLUSION: Present observations suggest that the combination of PLD with hyperthermia of skin metastases of breast carcinoma may be an active and well tolerated treatment.     

Synchronous bilateral male breast cancer: a case report

Synchronous bilateral breast cancer is extremely rare in men and has not, up to date, been reported in Korea. A 54-year-old man presented with a palpable mass in the right breast. The right nipple was retracted and bilateral axillary accessory breasts and nipples were present. On physical examination, a 2 cm-sized mass was palpated directly under the right nipple, and, with squeezing, bloody discharge developed in a single duct of the left nipple. There was no palpable mass in the left breast, and axillary lymph nodes were not palpable. Physical examination of external genitalia revealed a unilateral undescended testis on the left side. Synchronous bilateral breast cancer was diagnosed using mammography, ultrasonography, and core-needle biopsy. Histopathological examination revealed invasive ductal carcinoma in the right breast and ductal carcinoma in situ in the left breast. Bilateral total mastectomy, sentinel lymph node biopsy, and excision of accessory breasts in the axilla were performed.     

Gastric metastases from breast cancer: a case report

We describe a case of a 50 year old woman with a secondary involvement of the stomach from breast carcinoma. She complained of nausea, vomiting and epigastric pain resistant to gastroprotective drugs. Initially symptoms were attributed to the side effects of chemotherapeutic agents. Correct diagnosis led to effective treatment of gastrointestinal symptoms with consequent improvement in her quality of life.